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

Flavor changing t -> c l_1^- l_2^+ decay in the general two Higgs doublet model

We study the flavor changing t-> c l_1^- l_2^+ decay in the framework of the general two Higgs doublet model, the so called model III. We predict the branching ratio for l_1=\tau, l_2=\mu at the order of magnitude of BR \sim 10^{-8}.Comment: 12 Pages, 5 Figure

Single Top Quark Production via FCNC Couplings at Hadron Colliders

We calculate single top-quark production at hadron colliders via the chromo-magnetic flavor-changing neutral current couplings $\bar tcg$ and $\bar tug$. We find that the strength for the anomalous $\bar tcg$ ($\bar tug$) coupling may be probed to $\kappa_c / \Lambda = 0.092 {TeV}^{-1}$ ($\kappa_u / \Lambda = 0.026 {TeV}^{-1}$) at the Tevatron with $2 {fb}^{-1}$ of data and $\kappa_c / \Lambda = 0.013 {TeV}^{-1}$ ($\kappa_u / \Lambda = 0.0061 {TeV}^{-1}$) at the LHC with $10 {fb}^{-1}$ of data. The two couplings may be distinguished by a comparision of the single top signal with the direct top and top decay signals for these couplings.Comment: 18 pages, 6 figures, 3 table

Probing Topcolor-Assisted Technicolor from Top-Charm Associated Production at LHC

We propose to probe the topcolor-assisted technicolor (TC2) model from the top-charm associated productions at the LHC, which are highly suppressed in the Standard Model. Due to the flavor-changing couplings of the top quark with the scalars (top-pions and top-Higgs) in TC2 model, the top-charm associated productions can occur via both the s-channel and t-channel parton processes by exchanging a scalar field at the LHC. We examined these processes through Monte Carlo simulation and found that they can reach the observable level at the LHC in quite a large part of the parameter space of the TC2 model.Comment: Version to appear in PRD (Rapid Communication

Single top production at the LHC as a probe of R parity violation

We investigate the potential of the LHC to probe the R parity violating couplings involving the third generation by considering single top production. This study is based on particle level event generation for both signal and background, interfaced to a simplified simulation of the ATLAS detector.Comment: 11 pages, 5 figures, 5 tables (LaTeX, style revtex), few references adde

Dimension-six CP-conserving operators of the third-family quarks and their effects on collider observables

We list all possible dimension-six CP-conserving $SU_c(3)\times SU_L(2) \times U_Y(1)$ 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 $Wt\bar b$, $Xb\bar b$ and $Xt\bar t$ $( X=Z,\gamma,g,H)$ are presented. Analytic expressions for the tree level contributions of all these operators to the observables $R_b$ and $A^b_{FB}$ at LEP I, $\sigma(e^+e^-\rightarrow b\bar b)$ and $A^b_{FB}$ at LEP II, $\sigma(e^+e^-\rightarrow t\bar t)$ and $A_{FB}^t$ at the NLC, as well as $\sigma(p\bar p\rightarrow t\bar b+X)$ 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 $R_b$ and $A^b_{FB}$ 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

Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker

BACKGROUND: To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies. METHODS: The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up. RESULTS: Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor. CONCLUSION: Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention

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