6,891 research outputs found
Overexpression of Arabidopsis FLOWERING LOCUS T (FT) gene improves floral development in cassava (Manihot esculenta, Crantz)
Cassava is a tropical storage-root crop that serves as a worldwide source of staple food for over 800 million people. Flowering is one of the most important breeding challenges in cassava because in most lines flowering is late and non-synchronized, and flower production is sparse. The FLOWERING LOCUS T (FT) gene is pivotal for floral induction in all examined angiosperms. The objective of the current work was to determine the potential roles of the FT signaling system in cassava. The Arabidopsis thaliana FT gene (atFT) was transformed into the cassava cultivar 60444 through Agrobacterium-mediated transformation and was found to be overexpressed constitutively. FT overexpression hastened flower initiation and associated fork-type branching, indicating that cassava has the necessary signaling factors to interact with and respond to the atFT gene product. In addition, overexpression stimulated lateral branching, increased the prolificacy of flower production and extended the longevity of flower development. While FT homologs in some plant species stimulate development of vegetative storage organs, atFT inhibited storage-root development and decreased root harvest index in cassava. These findings collectively contribute to our understanding of flower development in cassava and have the potential for applications in breeding
Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis
Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments
Prevalence and genetic characteristics of Staphylococcus aureus CC398 isolates from invasive infections in spanish hospitals, focusing on the livestock-independent CC398-MSSA clade
Background: Livestock-associated (LA)-CC398-MRSA is closely related to pigs, being unfrequently detected in human invasive infections. CC398-MSSA is emerging in human invasive infections in some countries, but genetic and epidemiological characteristics are still scarcely reported.
Objectives: To determine the prevalence of Staphylococcus aureus (SA) CC398, both MRSA and MSSA, among blood cultures SA isolates recovered in Spanish hospitals located in regions with different pig-farming densities (PD) and characterize the recovered isolates.
Methods: One thousand twenty-two SA isolates (761 MSSA, 261 MRSA) recovered from blood cultures during 6–12 months in 17 Spanish hospitals (2018–2019) were studied. CC398 lineage identification, detection of spa-types, and antibiotic resistance, virulence and human immune evasion cluster (IEC) genes were analyzed by PCR/sequencing.
Results: Forty-four CC398-MSSA isolates (4.3% of SA; 5.8% of MSSA) and 10 CC398-MRSA isolates (1% of SA; 3.8% of MRSA) were detected. Eleven spa-types were found among the CC398-MSSA isolates with t571 and t1451 the most frequent spa-types detected (75%). Most of CC398-MSSA isolates were Immune-Evasion-Cluster (IEC)-positive (88.6%), tetracycline-susceptible (95.5%) and erythromycin/clindamycin–inducible-resistant/erm(T)-positive (75%). No statistical significance was detected when the CC398-MSSA/MSSA rate was correlated to PD (pigs/km2) (p = 0.108). On the contrary, CC398-MRSA isolates were all IEC-negative, predominately spa-t011 (70%), and the CC398-MRSA/MRSA rate was significantly associated to PD (p < 0.005).
Conclusion: CC398-MSSA is an emerging clade in invasive infections in Spanish hospitals. CC398-MRSA (mostly t011) and CC398-MSSA (mostly t571 and t1451) show important differences, possibly suggesting divergent steps in host-adaptation evolutionary processes. While CC398-MRSA is livestock-associated (lacking IEC-system), CC398-MSSA seems to be mostly livestock-independent, carrying human-adaptation markers.
Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis.
Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.The authors acknowledge funding from the National Institute of Allergy and Infectious Diseases (M.P.P. and M.N., R01AI114685; M.P.P., 1R21AI127594, R01AI124046; C.R.C., R21AI126296; https://www.niaid.nih.gov/), the Spanish Ministerio de Economí a, Industria y Competitividad (M.N., SAF2015-71444-P; D.G.-P., SAF2016-79957-R; http://www.mineco.gob.es), Subdireccion General de Redes ́ y Centros de Investigacion Cooperativa (RICET, https://www.ricet.es/) (M.N., RD16/0027/0019; D.G.P., RD16/ 0027/0014), and RTI2018-097210-B-I00 (MINCIU-FEDER) to F.G. An ACS MEDI Predoctoral Fellowship for D.M.K. is gratefully acknowledged, as is support from the National Science Foundation for K.F. (CHE-1262734). We thank AstraZeneca, Charles River Laboratories, and GlaxoSmithKline for the provision of the in vitro ADME and physicochemical properties data. The use of JChem/ChemAxon software is acknowledged
Search for the Higgs boson in events with missing transverse energy and b quark jets produced in proton-antiproton collisions at s**(1/2)=1.96 TeV
We search for the standard model Higgs boson produced in association with an
electroweak vector boson in events with no identified charged leptons, large
imbalance in transverse momentum, and two jets where at least one contains a
secondary vertex consistent with the decay of b hadrons. We use ~1 fb-1
integrated luminosity of proton-antiproton collisions at s**(1/2)=1.96 TeV
recorded by the CDF II experiment at the Tevatron. We find 268 (16) single
(double) b-tagged candidate events, where 248 +/- 43 (14.4 +/- 2.7) are
expected from standard model background processes. We place 95% confidence
level upper limits on the Higgs boson production cross section for several
Higgs boson masses ranging from 110 GeV/c2 to 140 GeV/c2. For a mass of 115
GeV/c2 the observed (expected) limit is 20.4 (14.2) times the standard model
prediction.Comment: 8 pages, 2 figures, submitted to Phys. Rev. Let
Precision Top-Quark Mass Measurements at CDF
We present a precision measurement of the top-quark mass using the full
sample of Tevatron TeV proton-antiproton collisions collected
by the CDF II detector, corresponding to an integrated luminosity of 8.7
. Using a sample of candidate events decaying into the
lepton+jets channel, we obtain distributions of the top-quark masses and the
invariant mass of two jets from the boson decays from data. We then compare
these distributions to templates derived from signal and background samples to
extract the top-quark mass and the energy scale of the calorimeter jets with
{\it in situ} calibration. The likelihood fit of the templates from signal and
background events to the data yields the single most-precise measurement of the
top-quark mass, \mtop = 172.85 \pm\pmComment: submitted to Phys. Rev. Let
Determination of the b quark mass at the M_Z scale with the DELPHI detector at LEP
An experimental study of the normalized three-jet rate of b quark events with
respect to light quarks events (light= \ell \equiv u,d,s) has been performed
using the CAMBRIDGE and DURHAM jet algorithms. The data used were collected by
the DELPHI experiment at LEP on the Z peak from 1994 to 2000. The results are
found to agree with theoretical predictions treating mass corrections at
next-to-leading order. Measurements of the b quark mass have also been
performed for both the b pole mass: M_b and the b running mass: m_b(M_Z). Data
are found to be better described when using the running mass. The measurement
yields: m_b(M_Z) = 2.85 +/- 0.18 (stat) +/- 0.13 (exp) +/- 0.19 (had) +/- 0.12
(theo) GeV/c^2 for the CAMBRIDGE algorithm. This result is the most precise
measurement of the b mass derived from a high energy process. When compared to
other b mass determinations by experiments at lower energy scales, this value
agrees with the prediction of Quantum Chromodynamics for the energy evolution
of the running mass. The mass measurement is equivalent to a test of the
flavour independence of the strong coupling constant with an accuracy of 7
permil.Comment: 24 pages, 10 figures, Accepted by Eur. Phys. J.
First Measurement of the W Boson Mass in Run II of the Tevatron
We present a measurement of the W boson mass using 200/pb of data collected
in pbar p collisions at sqrt(s) = 1.96 TeV by the CDF II detector at Run II of
the Fermilab Tevatron. With a sample of 63964 W -> e nu candidates and 51128 W
-> mu nu candidates, we measure M_W = (80413 +- 34 (stat) +- 34 (syst) = 80413
+- 48) MeV/c^2. This is the most precise single measurement of the W boson mass
to date.Comment: published version in PR
Observation and Mass Measurement of the Baryon
We report the observation and measurement of the mass of the bottom, strange
baryon through the decay chain , where
, , and .
Evidence for observation is based on a signal whose probability of arising from
the estimated background is 6.6 x 10^{-15}, or 7.7 Gaussian standard
deviations. The mass is measured to be (stat.) (syst.) MeV/.Comment: Minor text changes for the second version. Accepted by Phys. Rev.
Let
Search for New Particles Leading to Z+jets Final States in Collisions at TeV
We present the results of a search for new particles that lead to a \Z boson
plus jets in collisions at TeV using the Collider
Detector at Fermilab (CDF II). A data sample with a luminosity of 1.06 \ifb\
collected using \Z boson decays to and is used. We describe a
completely data-based method to predict the dominant background from
standard-model \Z+jet events. This method can be similarly applied to other
analyses requiring background predictions in multi-jet environments, as shown
when validating the method by predicting the background from +jets in \ttbar
production. No significant excess above the background prediction is observed,
and a limit is set using a fourth generation quark model to quantify the
acceptance. Assuming and using a leading-order
calculation of the cross section, quark masses below 268 \gev/c^2
are excluded at 95% confidence level.Comment: To be submitted to PR
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