Plasmodium falciparum PhIL1-associated complex plays an essential role in merozoite reorientation and invasion of host erythrocytes.

The human malaria parasite, Plasmodium falciparum possesses unique gliding machinery referred to as the glideosome that powers its entry into the insect and vertebrate hosts. Several parasite proteins including Photosensitized INA-labelled protein 1 (PhIL1) have been shown to associate with glideosome machinery. Here we describe a novel PhIL1 associated protein complex that co-exists with the glideosome motor complex in the inner membrane complex of the merozoite. Using an experimental genetics approach, we characterized the role(s) of three proteins associated with PhIL1: a glideosome associated protein- PfGAPM2, an IMC structural protein- PfALV5, and an uncharacterized protein-referred here as PfPhIP (PhIL1 Interacting Protein). Parasites lacking PfPhIP or PfGAPM2 were unable to invade host RBCs. Additionally, the downregulation of PfPhIP resulted in significant defects in merozoite segmentation. Furthermore, the PfPhIP and PfGAPM2 depleted parasites showed abrogation of reorientation/gliding. However, initial attachment with host RBCs was not affected in these parasites. Together, the data presented here show that proteins of the PhIL1-associated complex play an important role in the orientation of P. falciparum merozoites following initial attachment, which is crucial for the formation of a tight junction and hence invasion of host erythrocytes

GlmS mediated knock-down of a phospholipase expedite alternate pathway to generate phosphocholine required for phosphatidylcholine synthesis in Plasmodium falciparum

Phospholipid synthesis is crucial for membrane proliferation in malaria parasites during the entire cycle in the host cell. The major phospholipid of parasite membranes, phosphatidylcholine (PC), is mainly synthesized through the Kennedy pathway. The phosphocholine required for this synthetic pathway is generated by phosphorylation of choline derived from the catabolism of the lyso-phosphatidylcholine (LPC) scavenged from the host milieu. Here we have characterized a Plasmodium falciparum lysophospholipase (PfLPL20) which showed enzymatic activity on LPC substrate to generate choline. Using GFP- targeting approach, PfLPL20 was localized in vesicular structures associated with the neutral lipid storage bodies present juxtaposed to the food-vacuole. The C-terminal tagged glmS mediated inducible knock-down of PfLPL20 caused transient hindrance in the parasite development, however, the parasites were able to multiply efficiently, suggesting that PfLPL20 is not essential for the parasite. However, in PfLPL20 depleted parasites, transcript levels of enzyme of SDPM pathway (Serine Decarboxylase-Phosphoethanolamine Methyltransferase) were altered along with up-regulation of phosphocholine and SAM levels; these results show up-regulation of alternate pathway to generate the phosphocholine required for PC synthesis through the Kennedy pathway. Our study highlights the presence of alternate pathways for lipid homeostasis/membrane-biogenesis in the parasite; these data could be useful to design future therapeutic approaches targeting phospholipid metabolism in the parasite

A Plasmodium falciparum lysophospholipase regulates fatty acid acquisition for membrane biogenesis to enable schizogonic asexual division

Phospholipid metabolism is crucial for membrane biogenesis and homeostasis during the intracellular life cycle of Plasmodium falciparum. To generate large amounts of phospholipids required during blood stages, the parasite massively scavenge, recycle and reassemble host lipids. P. falciparum possesses an unusual large number of lysophospholipases. However, their functional roles and importance remain to be elucidated. Here, we functionally characterized one of P. falciparum lysophospholipase (PfLPL3) (Gene ID PF3D7_1476800), to reveal its critical role in parasite propagation during asexual blood stages. We generated a transgenic parasite line using GFP-glmS C-terminal tagging approach, for localization as well as inducible knockdown of PfLPL3. PfLPL3 displayed a dynamic localization throughout asexual stages, mainly localizing in the host parasite interface: parasitophorous vacuole space and expanding into the tubulovesicular network within the host cell. Inducible knock-down of PfLPL3 hindered normal intraerythrocytic cycle, specifically causing disruption in parasite development from trophozoites to schizont, as well as reduction in number of merozoites progenies. Thus, down-regulation of PfLPL3 significantly inhibited parasite growth suggesting its critical role for proper parasite propagation during blood stages. Detailed lipidomic analyses showed that PfLPL3 generates fatty-acids for the synthesis of neutral lipids DAG and TAG, whilst controlling the timely synthesis of phospholipids that are crucial for membrane biogenesis required for merozoite development during asexual cycle. Setting up an in vitro activity based screening of Malaria Box allowed identification of specific inhibitors of PfLPL3 having potent parasitical efficacies. These compounds are pertinent both as anti-malarial drug candidates and chemical tools specifically targeting membrane biogenesis during asexual blood stages

Search for CPCP violation in D0^0→\to KS0^0_\mathrm{S}KS0^0_\mathrm{S} decays in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search is reported for charge-parity D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ violation in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ decays, using data collected in proton-proton collisions at $\sqrt{s}$ = 13 TeV recorded by the CMS experiment in 2018. The analysis uses a dedicated data set that corresponds to an integrated luminosity of 41.6 fb$^{-1}$, which consists of about 10 billion events containing a pair of ẖadrons, nearly all of which decay to charm hadrons. The flavor of the neutral D meson is determined by the pion charge in the reconstructed decays D$^{*+}$$\to$ D$^0\pi^+$ and D$^{*-}$$\to$ D$^0\pi^-$. The D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ asymmetry in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ is measured to be $A_{CP}$( K$^0_\mathrm{S}$K$^0_\mathrm{S}$) = (6.2 $\pm$ 3.0 $\pm$ 0.2 $\pm$ 0.8)%, where the three uncertainties represent the statistical uncertainty, the systematic uncertainty, and the uncertainty in the measurement of the D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry in the D$^0$ $\to$ K$^0_\mathrm{S}\pi^+\pi^-$ decay. This is the first D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry measurement by CMS in the charm sector as well as the first to utilize a fully hadronic final state

Measurement of inclusive and differential cross sections for W+^{+}W−^{-} production in proton-proton collisions at s= \sqrt{s} = 13.6 TeV

Measurements at $\sqrt{s}=$ 13.6 TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8 fb$^{-1}$. Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavour and charge of the leptons, the number of jets, and number of jets originating from b quarks. An inclusive W$^{+}$W$^{-}$ production cross section of 125.7 $\pm$ 5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector acceptance, both inclusively and differentially, as a function of the jet multiplicity in the event. For first time in proton-proton collisions, WW events with at least two reconstructed jets are studied and compared with recent theoretical predictions.Measurements at $\sqrt{s}$ = 13.6 TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8 fb$^{-1}$. Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavour and charge of the leptons, the number of jets, and number of jets originating from b quarks. An inclusive W$^+$W$^-$ production cross section of 125.7 $\pm$ 5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector acceptance, both inclusively and differentially, as a function of the jet multiplicity in the event. For first time in proton-proton collisions, WW events with at least two reconstructed jets are studied and compared with recent theoretical predictions

Observation of the J/ψ\psi →\to μ+μ−μ+μ−\mu^+\mu^-\mu^+\mu^- decay in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe J/$\psi$$\to$$\mu^+\mu^-\mu^+\mu^-$ decay has been observed with a statistical significance in excess of five standard deviations. The analysis is based on an event sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of 33.6 fb${-1}$. Normalizing to the J/$\psi$$\to$$\mu^+\mu^-$ decay mode leads to a branching fraction [10.1$^{+3.3}_{-2.7}$ (stat) $\pm$ 0.4 (syst) ]$\times$ 10$^{-7}$, a value that is consistent with the standard model prediction

Enriching the physics program of the CMS experiment via data scouting and data parking

International audienceSpecialized data-taking and data-processing techniques were introduced by the CMS experiment in Run 1 of the CERN LHC to enhance the sensitivity of searches for new physics and the precision of standard model measurements. These techniques, termed data scouting and data parking, extend the data-taking capabilities of CMS beyond the original design specifications. The novel data-scouting strategy trades complete event information for higher event rates, while keeping the data bandwidth within limits. Data parking involves storing a large amount of raw detector data collected by algorithms with low trigger thresholds to be processed when sufficient computational power is available to handle such data. The research program of the CMS Collaboration is greatly expanded with these techniques. The implementation, performance, and physics results obtained with data scouting and data parking in CMS over the last decade are discussed in this Report, along with new developments aimed at further improving low-mass physics sensitivity over the next years of data taking

Observation of the J/ψ\psi→\toμ+μ−μ+μ−\mu^+\mu^-\mu^+\mu^- decay in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe J/$\psi$$\to$$\mu^+\mu^-\mu^+\mu^-$ decay has been observed with a statistical significance in excess of five standard deviations. The analysis is based on an event sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of 33.6 fb${-1}$. Normalizing to the J/$\psi$$\to$$\mu^+\mu^-$ decay mode leads to a branching fraction [10.1$^{+3.3}_{-2.7}$ (stat) $\pm$ 0.4 (syst) ]$\times$ 10$^{-7}$, a value that is consistent with the standard model prediction

Search for a resonance decaying to a W boson and a photon in proton-proton collisions at s= \sqrt{s} = 13 TeV using leptonic W boson decays

A search for a new charged particle X with mass between 0.3 and 2.0 TeV decaying to a W boson and a photon is presented, using proton-proton collision data at a center-of-mass energy of 13 TeV, collected by the CMS experiment and corresponding to an integrated luminosity of 138 fb$^{-1}$. Particle X has electric charge $\pm$1 and is assumed to have spin 0. The search is performed using the electron and muon decays of the W boson. No significant excess above the predicted background is observed. The upper limit at 95% confidence level on the product of the production cross section of the X and its branching fraction to a W boson and a photon is found to be 94 (137) fb for a 0.3 TeV resonance and 0.75 (0.81) fb for a 2.0 TeV resonance, for an X width-to-mass ratio of 0.01% (5%). This search presents the most stringent constraints to date on the existence of such resonances across the probed mass range. A statistical combination with an earlier study based on the hadronic decay mode of the W boson is also performed, and the upper limit at 95% confidence level for a 2.0 TeV resonance is reduced to 0.50 (0.63) fb for an X width-to-mass ratio of 0.01% (5%).A search for a new charged particle X with mass between 0.3 and 2.0 TeV decaying to a W boson and a photon is presented, using proton-proton collision data at a center-of-mass energy of 13 TeV, collected by the CMS experiment and corresponding to an integrated luminosity of 138 fb$^{-1}$. Particle X has electric charge $\pm$1 and is assumed to have spin 0. The search is performed using the electron and muon decays of the W boson. No significant excess above the predicted background is observed. The upper limit at 95% confidence level on the product of the production cross section of the X and its branching fraction to a W boson and a photon is found to be 94 (137) fb for a 0.3 TeV resonance and 0.75 (0.81) fb for a 2.0 TeV resonance, for an X width-to-mass ratio of 0.01% (5%). This search presents the most stringent constraints to date on the existence of such resonances across the probed mass range. A statistical combination with an earlier study based on the hadronic decay mode of the W boson is also performed, and the upper limit at 95% confidence level for a 2.0 TeV resonance is reduced to 0.50 (0.63) fb for an X width-to-mass ratio of 0.01% (5%)

Search for CP violation in D0→KS0KS0 \mathrm{D^0}\to\mathrm{K^0_S}\mathrm{K^0_S} decays in proton-proton collisions at s= \sqrt{s} = 13 TeV

A search is reported for charge-parity CP violation in $\mathrm{D^0}\to\mathrm{K^0_S}\mathrm{K^0_S}$ decays, using data collected in proton-proton collisions at $\sqrt{s} =$ 13 TeV recorded by the CMS experiment in 2018. The analysis uses a dedicated data set that corresponds to an integrated luminosity of 41.6 fb$^{-1}$, which consists of about 10 billion events containing a pair of b hadrons, nearly all of which decay to charm hadrons. The flavor of the neutral $\mathrm{D}$ meson is determined by the pion charge in the reconstructed decays $\mathrm{D}^{*+}\to\mathrm{D^0}\pi^{+}$ and $\mathrm{D}^{*-}\to\overline{\mathrm{D}}^{0}\pi^{-}$. The CP asymmetry in $\mathrm{D^0}\to\mathrm{K^0_S}\mathrm{K^0_S}$ is measured to be $A_{CP}(\mathrm{K^0_S}\mathrm{K^0_S}) =$ (6.2 $\pm$ 3.0 $\pm$ 0.2 $\pm$ 0.8)%, where the three uncertainties represent the statistical uncertainty, the systematic uncertainty, and the uncertainty in the measurement of the CP asymmetry in the $\mathrm{D^0}\to\mathrm{K^0_S}\pi^{+}\pi^{-}$ decay. This is the first CP asymmetry measurement by CMS in the charm sector as well as the first to utilize a fully hadronic final state.A search is reported for charge-parity D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ violation in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ decays, using data collected in proton-proton collisions at $\sqrt{s}$ = 13 TeV recorded by the CMS experiment in 2018. The analysis uses a dedicated data set that corresponds to an integrated luminosity of 41.6 fb$^{-1}$, which consists of about 10 billion events containing a pair of ẖadrons, nearly all of which decay to charm hadrons. The flavor of the neutral D meson is determined by the pion charge in the reconstructed decays D$^{*+}$$\to$ D$^0\pi^+$ and D$^{*-}$$\to$ D$^0\pi^-$. The D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ asymmetry in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ is measured to be $A_{CP}$( K$^0_\mathrm{S}$K$^0_\mathrm{S}$) = (6.2 $\pm$ 3.0 $\pm$ 0.2 $\pm$ 0.8)%, where the three uncertainties represent the statistical uncertainty, the systematic uncertainty, and the uncertainty in the measurement of the D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry in the D$^0$ $\to$ K$^0_\mathrm{S}\pi^+\pi^-$ decay. This is the first D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry measurement by CMS in the charm sector as well as the first to utilize a fully hadronic final state