117 research outputs found
Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein
BACKGROUND: We previously described the selection of a T20-dependent human immunodeficiency virus type-1 (HIV-1) variant in a patient on T20 therapy. The fusion inhibitor T20 targets the viral envelope (Env) protein by blocking a conformational switch that is critical for viral entry into the host cell. T20-dependent viral entry is the result of 2 mutations in Env (GIA-SKY), creating a protein that undergoes a premature conformational switch, and the presence of T20 prevents this premature switch and rescues viral entry. In the present study, we performed 6 independent evolution experiments with the T20-dependent HIV-1 variant in the absence of T20, with the aim to identify second site compensatory changes, which may provide new mechanistic insights into Env function and the T20-dependence mechanism. RESULTS: Escape variants with improved replication capacity appeared within 42 days in 5 evolution cultures. Strikingly, 3 cultures revealed the same single amino acid change in the CD4 binding region of Env (glycine at position 431 substituted for arginine: G431R). This mutation was sufficient to abolish the T20-dependence phenotype and restore viral replication in the absence of T20. The GIA-SKY-G431R escape variant produces an Env protein that exhibits reduced syncytia formation and reduced cell-cell fusion activity. The escape variant was more sensitive to an antibody acting on an early gp41 intermediate, suggesting that the G431R mutation helps preserve a pre-fusion Env conformation, similar to T20 action. The escape variant was also less sensitive to soluble CD4, suggesting a reduced CD4 receptor affinity. CONCLUSION: The forced evolution experiments indicate that the premature conformational switch of the T20-dependent HIV-1 Env variant (GIA-SKY) can be corrected by a second site mutation in Env (GIA-SKY-G431R) that affects the interaction with the CD4 receptor
Lactobacillus fermentum ME-3 – an antimicrobial and antioxidative probiotic
The paper lays out the short scientific history and characteristics of the new probiotic Lactobacillus fermentum strain ME-3 DSM-14241, elaborated according to the regulations of WHO/FAO (2002). L. fermentum ME-3 is a unique strain of Lactobacillus species, having at the same time the antimicrobial and physiologically effective antioxidative properties and expressing health-promoting characteristics if consumed. Tartu University has patented this strain in Estonia (priority June 2001, patent in 2006), Russia (patent in 2006) and the USA (patent in 2007). The paper describes the process of the identification and molecular typing of this probiotic strain of human origin, its deposition in an international culture collection, and its safety assessment by laboratory tests and testing on experimental animals and volunteers. It has been established that L. fermentum strain ME-3 has double functional properties: antimicrobial activity against intestinal pathogens and high total antioxidative activity (TAA) and total antioxidative status (TAS) of intact cells and lysates, and it is characterized by a complete glutathione system: synthesis, uptake and redox turnover. The functional efficacy of the antimicrobial and antioxidative probiotic has been proven by the eradication of salmonellas and the reduction of liver and spleen granulomas in Salmonella Typhimurium-infected mice treated with the combination of ofloxacin and L. fermentum strain ME-3. Using capsules or foodstuffs enriched with L. fermentum ME-3, different clinical study designs (including double-blind, placebo-controlled, crossover studies) and different subjects (healthy volunteers, allergic patients and those recovering from a stroke), it has been shown that this probiotic increased the antioxidative activity of sera and improved the composition of the low-density lipid particles (LDL) and post-prandial lipids as well as oxidative stress status, thus demonstrating a remarkable anti-atherogenic effect. The elaboration of the probiotic L. fermentum strain ME-3 has drawn on wide international cooperative research and has taken more than 12 years altogether. The new ME-3 probiotic-containing products have been successfully marketed and sold in Baltic countries and Finland
Test of lepton universality in decays
The first simultaneous test of muon-electron universality using
and decays is performed, in two ranges of the dilepton
invariant-mass squared, . The analysis uses beauty mesons produced in
proton-proton collisions collected with the LHCb detector between 2011 and
2018, corresponding to an integrated luminosity of 9 . Each
of the four lepton universality measurements reported is either the first in
the given interval or supersedes previous LHCb measurements. The
results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-046.html (LHCb
public pages
Precision measurement of violation in the penguin-mediated decay
A flavor-tagged time-dependent angular analysis of the decay
is performed using collision data collected
by the LHCb experiment at % at TeV, the center-of-mass energy of
13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The
-violating phase and direct -violation parameter are measured
to be rad and
, respectively, assuming the same values
for all polarization states of the system. In these results, the
first uncertainties are statistical and the second systematic. These parameters
are also determined separately for each polarization state, showing no evidence
for polarization dependence. The results are combined with previous LHCb
measurements using collisions at center-of-mass energies of 7 and 8 TeV,
yielding rad and . This is the most precise study of time-dependent violation
in a penguin-dominated meson decay. The results are consistent with
symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb
public pages
First observation of a doubly charged tetraquark and its neutral partner
A combined amplitude analysis is performed for the decays and , which are
related by isospin symmetry. The analysis is based on data collected by the
LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8
and 13. The full data sample corresponds to an integrated
luminosity of 9. Two new resonant states with masses of
and widths of
are observed, which decay to and
respectively. The former state indicates the first observation of
a doubly charged open-charm tetraquark state with minimal quark content
, and the latter state is a neutral tetraquark composed of
quarks. Both states are found to have spin-parity ,
and their resonant parameters are consistent with each other, which suggests
that they belong to an isospin triplet.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-026.html (LHCb
public pages
Observation of a resonant structure near the threshold in the decay
An amplitude analysis of the decay is carried out to
study for the first time its intermediate resonant contributions, using
proton-proton collision data collected with the LHCb detector at centre-of-mass
energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as
, is observed in the invariant-mass spectrum with
significance greater than 12 standard deviations. The mass, width and the
quantum numbers of the structure are measured to be MeV,
MeV and , respectively, where the first
uncertainties are statistical and the second systematic. The properties of the
new structure are consistent with recent theoretical predictions for a state
composed of quarks. Evidence for an additional structure is
found around 4140 MeV in the invariant mass, which might be
caused either by a new resonance with the assignment or by a coupled-channel effect.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-018.html (LHCb
public pages
Measurement of the differential branching fraction
The branching fraction of the rare decay is measured for the first time, in the squared dimuon mass
intervals, , excluding the and regions. The data
sample analyzed was collected by the LHCb experiment at center-of-mass energies
of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\
\mathrm{fb}^{-1}q^{2}q^{2} >15.0\
\mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model
dependence, agrees with the predictions.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-050.html (LHCb
public pages
Precise determination of the B-s(0)-B-s(-0) oscillation frequency
Mesons comprising a beauty quark and a strange quark can oscillate between
particle (B0s) and antiparticle (B0s) flavour eigenstates, with a frequency
given by the mass difference between heavy and light mass eigenstates, deltams.
Here we present ameasurement of deltams using B0s2DsPi decays produced in
proton-proton collisions collected with the LHCb detector at the Large Hadron
Collider. The oscillation frequency is found to be deltams = 17.7683 +- 0.0051
+- 0.0032 ps-1, where the first uncertainty is statistical and the second
systematic. This measurement improves upon the current deltams precision by a
factor of two. We combine this result with previous LHCb measurements to
determine deltams = 17.7656 +- 0.0057 ps-1, which is the legacy measurement of
the original LHCb detector.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2021-005.html (LHCb
public pages
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