110 research outputs found
Whole-genome sequencing for One Health surveillance of antimicrobial resistance in conflict zones: a case study of Salmonella spp. and Campylobacter spp. in the West Bank, Palestine
Antimicrobial resistance (AMR) is a critical global concern driven by the overuse, misuse, and/or usage of inadequate antibiotics on humans, animals' agriculture, and as a result of contaminated environments. This study is the first One Health survey in the Middle East that incorporated whole-genome sequencing (WGS) to examine the spread of AMR in Campylobacter spp. and Salmonella spp. This cross-sectional study was conducted to examine the role of AMR at the human-animal-environmental interface and was performed in Ramallah/Al-Bireh and Jerusalem governorates of the central West Bank, Palestine. In 2021 and 2022, a total of 592 samples were collected and analyzed. From a total of 65 Campylobacter jejuni and 19 Salmonella spp. isolates, DNA was extracted for WGS using Oxford Nanopore Technologies MinION platform. We found that the dominant serotypes of C. jejuni and Salmonella enterica were present in chicken manure, chicken meat sold in markets, and feces of asymptomatic farm workers, with high genetic similarities between the isolates regardless of origin. Additionally, our results showed rapid strain turnover in C. jejuni from the same sites between 2021 and 2022. Most of the positive Salmonella spp. samples were multidrug-resistant (MDR) S. enterica serovar Muenchen carrying the plasmid of emerging S. infantis (pESI) megaplasmid, conferring resistance to multiple antibiotics. Our findings highlight the spread of MDR foodborne pathogens from animals to humans through the food chain, emphasizing the importance of a One Health approach that considers the interconnections between human, animal, and environmental health. IMPORTANCE Prior to this study, there existed hardly an integrated human-animal-environmental study of Salmonellosis and Campylobacteriosis and related AMR in Middle Eastern countries. The few existing studies lack robust epidemiological study designs, adequate for a One Health approach, and did not use WGS to determine the circulating serotypes and their AMR profiles. Civil unrest and war in Middle Eastern countries drive AMR because of the breakdown of public health and food security services. This study samples simultaneously humans, animals, and the environment to comprehensively investigate foodborne pathogens in the broiler chicken production chain in Palestine using WGS. We show that identical serotypes of C. jejuni and S. enterica can be found in samples from chicken farms, chicken meat sold in markets, and asymptomatic broiler chicken production workers. The most striking feature is the rapid dynamic of change in the genetic profile of the detected species in the same sampling locations. The majority of positive Salmonella spp. samples are MDR S. enterica serovar Muenchen isolates carrying the pESI megaplasmid. The results demonstrate a close relationship between the S. enterica serovar Muenchen isolates found in our sample collection and those responsible for 40% of all clinical Salmonella spp. isolates in Israel as previously reported, with a sequence identity of over 99.9%. These findings suggest the transboundary spread of MDR S. enterica serovar Muenchen strains from animals to humans through the food chain. The study underscores the importance of combining integrated One Health studies with WGS for detecting environmental-animal-human transmission of foodborne pathogens that could not be detected otherwise. This study showcases the benefits of integrated environmental-animal-human sampling and WGS for monitoring AMR. Environmental samples, which may be more accessible in conflict-torn places where monitoring systems are limited and regulations are weak, can provide an effective AMR surveillance solution. WGS of bacterial isolates provides causal inference of the distribution and spread of bacterial serotypes and AMR in complex social-ecological systems. Consequently, our results point toward the expected benefits of operationalizing a One Health approach through closer cooperation of public and animal health and food safety authorities
Dimension-six CP-conserving operators of the third-family quarks and their effects on collider observables
We list all possible dimension-six CP-conserving invariant operators involving the third-family quarks which
could be generated by new physics at a higher scale. Expressions for these
operators after electroweak gauge symmetry breaking and the induced effective
couplings , and are
presented. Analytic expressions for the tree level contributions of all these
operators to the observables and at LEP I,
and at LEP II,
and at the NLC, as well as
at the Tevatron upgrade, are provided.
The effects of these operators on different electroweak observables are
discussed and numerical examples presented. Numerical analyses show that in the
coupling region allowed by and at LEP I, some of the new
physics operators can still have significant contributions at LEP II, the
Tevatron and the NLC.Comment: 25 page
Genomic surveillance enables the identification of co-infections with multiple SARS-CoV-2 lineages in equatorial Guinea
COVID-19 disease caused by SARS-CoV-2 represents an ongoing global public health emergency. Rapid identification of emergence, evolution, and spread of SARS-CoV-2 variants of concern (VOC) would enable timely and tailored responses by public health decision-making bodies. Yet, global disparities in current SARS-CoV-2 genomic surveillance activities reveal serious geographical gaps. Here, we discuss the experiences and lessons learned from the SARS-CoV-2 monitoring and surveillance program at the Public Health Laboratory on Bioko Island, Equatorial Guinea that was implemented as part of the national COVID-19 response and monitoring activities. We report how three distinct SARS-CoV-2 variants have dominated the epidemiological situation in Equatorial Guinea since March 2020. In addition, a case of co-infection of two SARS-CoV-2 VOC, Beta and Delta, in a clinically asymptomatic and fully COVID-19 vaccinated man living in Equatorial Guinea is presented. To our knowledge, this is the first report of a person co-infected with Beta and Delta VOC globally. Rapid identification of co-infections is relevant since these might provide an opportunity for genetic recombination resulting in emergence of novel SARS-CoV-2 lineages with enhanced transmission or immune evasion potential
Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes
The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders
Calibration of myocardial T2 and T1 against iron concentration.
BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.
METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy.
RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001).
CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies
Top-Charm Associated Production in High Energy Collisions
The possibility of exploring the flavor changing neutral current
couplings in the production vertex for the reaction \epem\to
t\bar c + \bar tc is examined. Using a model independent parameterization for
the effective Lagrangian to describe the most general three-point interactions,
production cross sections are found to be relatively small at LEP II, but
potentially sizeable at higher energy \epem colliders. The kinematic
characteristics of the signal are studied and a set of cuts are devised for
clean separation of the signal from background. The resulting sensitivity to
anomalous flavor changing couplings at LEP II with an integrated luminosity of
pb is found to be comparable to their present indirect
constraints from loop processes, while at higher energy colliders with
TeV center-of-mass energy and 50-200 fb luminosity, one expects to reach
a sensitivity at or below the percentage level.Comment: Latex, 22 page
Measurement of the Helicity of W Bosons in Top Quark Decays
We use the transverse momentum spectrum of leptons in the decay chain t-->bW
with W-->l nu to measure the helicity of the W bosons in the top quark rest
frame. Our measurement uses a ttbar sample isolated in 106 +/- 4 inverse
picobarns of data collected in ppbar collisions at sqrt(s)=1.8 TeV with the CDF
detector at the Fermilab Tevatron. Assuming a standard V--A weak decay, we find
that the fraction of W's with zero helicity in the top rest frame is F_0 = 0.91
+/- 0.37 (stat) +/- 0.13 (syst), consistent with the standard model prediction
of F_0=0.70 for a top mass of 175 GeV/c**2.Comment: Submitted to PRL. 8 pages, 2 figure
Search for the Supersymmetric Partner of the Top-Quark in Collisions at
We report on a search for the supersymmetric partner of the top quark (stop)
produced in events using of
collisions at recorded with the Collider Detector at
Fermilab. In the case of a light stop squark, the decay of the top quark into
stop plus the lightest supersymmetric particle (LSP) could have a significant
branching ratio. The observed events are consistent with Standard Model production and decay. Hence, we set limits on the branching ratio of
the top quark decaying into stop plus LSP, excluding branching ratios above 45%
for a LSP mass up to 40 {\rm GeV/c}.Comment: 11 pages, 4 figure
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