Deficiency of Pkc1 activity affects glycerol metabolism in Saccharomyces cerevisiae

In pressProtein kinase C is apparently involved in the control of many cellular systems: the cell wall integrity pathway, the synthesis of ribosomes, the appropriated reallocation of transcription factors under specific stress conditions and also the regulation of N-glycosylation activity. All these observations suggest the existence of additional targets not yet identified. In the context of the control of carbon metabolism, previous data demonstrated that Pkc1 p might play a central role in the control of cellular growth and metabolism in yeast. In particular, it has been suggested that it might be involved in the derepression of genes under glucose-repression by driving an appropriated subcellular localization of transcriptional factors, such as Mig1 p. In this work, we show that pkc1∆ mutant is unable to grow on glycerol because it cannot perform the derepression of GUT1 gene that encodes for glycerol kinase. Additionally, active transport is also partially affected. Using this phenotype, we were able to isolate a new pkc1∆ revertant. We also isolated two transformants identified as the nuclear exportin Msn5 and the histone deacetylase Hos2 extragenic suppressors of this mutation. Based on these results, we postulate that Pkc1 p may be involved in the control of the cellular localization and/or regulation of the activity of nuclear proteins implicated in gene expression.Fundação Universidade Federal de Ouro Preto (FUFOP). Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) - CBS-1875/95. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - 300998/89-9 to R.L.B., 301255/01-6 to L.G.F

The design, implementation, and performance of the LZ calibration systems

LUX-ZEPLIN (LZ) is a tonne-scale experiment searching for direct dark matter interactions and other rare events. It is located at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. The core of the LZ detector is a dual-phase xenon time projection chamber (TPC), designed with the primary goal of detecting Weakly Interacting Massive Particles (WIMPs) via their induced low energy nuclear recoils. Surrounding the TPC, two veto detectors immersed in an ultra-pure water tank enable reducing background events to enhance the discovery potential. Intricate calibration systems are purposely designed to precisely understand the responses of these three detector volumes to various types of particle interactions and to demonstrate LZ's ability to discriminate between signals and backgrounds. In this paper, we present a comprehensive discussion of the key features, requirements, and performance of the LZ calibration systems, which play a crucial role in enabling LZ's WIMP-search and its broad science program. The thorough description of these calibration systems, with an emphasis on their novel aspects, is valuable for future calibration efforts in direct dark matter and other rare-event search experiments

New constraints on ultraheavy dark matter from the LZ experiment

Searches for dark matter with liquid xenon time projection chamber experiments have traditionally focused on the region of the parameter space that is characteristic of weakly interacting massive particles, ranging from a few GeV/c2 to a few TeV/c2. Models of dark matter with a mass much heavier than this are well motivated by early production mechanisms different from the standard thermal freeze-out, but they have generally been less explored experimentally. In this work, we present a reanalysis of the first science run of the LZ experiment, with an exposure of 0.9  tonne×yr, to search for ultraheavy particle dark matter. The signal topology consists of multiple energy deposits in the active region of the detector forming a straight line, from which the velocity of the incoming particle can be reconstructed on an event-by-event basis. Zero events with this topology were observed after applying the data selection calibrated on a simulated sample of signal-like events. New experimental constraints are derived, which rule out previously unexplored regions of the dark matter parameter space of spin-independent interactions beyond a mass of 1017  GeV/c2. Published by the American Physical Society 2024 </jats:sec

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Search for pair production of boosted Higgs bosons via vector-boson fusion in the bb¯bb¯ final state using pp collisions at √s = 13 TeV with the ATLAS detector

A search for Higgs boson pair production via vector-boson fusion is performed in the Lorentz-boosted regime, where a Higgs boson candidate is reconstructed as a single large-radius jet, using 140 fb−1 of proton–proton collision data at √s = 13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Only Higgs boson decays into bottom quark pairs are considered. The search is particularly sensitive to the quartic coupling between two vector bosons and two Higgs bosons relative to its Standard Model prediction, K2V . This study constrains K2V to 0.55 &lt; K2V &lt; 1.49 at the 95% confidence level. The value K2V = 0 is excluded with a significance of 3.8 standard deviations with other Higgs boson couplings fixed to their Standard Model values. A search for new heavy spin-0 resonances that would mediate Higgs boson pair production via vector-boson fusion is carried out in the mass range of 1–5 TeV for the first time under several model and decay-width assumptions. No significant deviation from the Standard Model hypothesis is observed and exclusion limits at the 95% confidence level are derived

Measurements of the production cross-section for a Z boson in association with b- or c-jets in proton–proton collisions at √s = 13 TeV with the ATLAS detector

This paper presents a measurement of the production cross-section of a Z boson in association with bor c-jets, in proton–proton collisions at √s = 13 TeV with the ATLAS experiment at the Large Hadron Collider using data corresponding to an integrated luminosity of 140 fb−1. Inclusive and differential cross-sections are measured for events containing a Z boson decaying into electrons or muons and produced in association with at least one b-jet, at least one c-jet, or at least two b-jets with transverse momentum pT > 20 GeV and rapidity |y| < 2.5. Predictions from several Monte Carlo generators based on next-to-leading-order matrix elements interfaced with a parton-shower simulation, with different choices of flavour schemes for initial-state partons, are compared with the measured cross-sections. The results are also compared with novel predictions, based on infrared and collinear safe jet flavour dressing algorithms. Selected Z+ ≥ 1 c-jet observables, optimized for sensitivity to intrinsic-charm, are compared with benchmark models with different intrinsic-charm fractions