Prevalence and Characterization of Some Colibactin Genes in Clinical Enterobacteriaceae isolates from Iraqi Patients

                افراد العائلة المعوية تمتلك مجموعة من الجينات تدعى Polyketide synthase (pks). هذه المجموعة من الجينات تكون مسؤولة عن تصنيع الذيفان الذي يطلق عليه Colibactin والذي له دور مهم في استحثاث تكسر اشرطة الدنا المزدوجة DNA والذي يؤدي الى استحثاث ورم او ما يعرف بسرطان القولون، احد عشر من اصل ثمانية وثمانين عزلة  بكتيرية وتمثل (12.5%) كانت قد توزعت 7(8%) عزلة تعود لبكتربا E. coli، 2(2.25%) عزلة تعود لبكتريا K. pneumonia و 2(2.25%) تعود لبكتريا E. aerogenes كانت حاملة لجينات الكولبكتين قيد الدراسة. تم اختبار لتأثير السمي الخلوي لعزلتين كانت موجبة للجينات قيد الدراسة وهي E. coli and E. aerogenes تجاه خط الخلايا السرطاني المعروف بـ HeLa  بينت النائج انخفاض عدد الخلايا وحصول استطالة في انوية الخلايامقارنة بالخلايا الغير معاملة. اظهرت النتائج حصول تغيرات نسيجية في الخلايا بأستخدام صبغة AO/EBr تم ملاحظتها بأستخدام المجهر الفلورسيني: بعض هذه التغيرات تم ملاحظتها في لون كروماتين النواة ومصحوب بتكثف الدنا النووي وكذلك حصول تكسر في النوية، خلايا الـ HeLa التي ظهرت بلون اخضر ولم تحصل فيها اي تغيرات في لون المادة الكروماتينية هي خلايا حية ولم تتم معاملتها مع البكتريا الحاملة للجينات قيد الدراسة، بينما الخلايا المعاملة مع خلايا بكتيرية حاملة للجينات ظهرت انويتها بلون برتقالي داكن وهي خلايا ميتة. يستنتج من ذلك ان عزلات البكتريا المعوية المعزولة من مرضى عراقيين يمكنها ان تفرز مواد سامة (ذيفان الكولبكتين) يمكنها قتل قتل الخلايا السرطانية نوع HeLa وهذا ناتج عن تغيرات حصلت في انوية الخلايا المعرضة للبكتريا وكان واضح في كثافة وتكسر المادة الوراثية للخلايا قيد الدراسة. The members of the family of Eentrobacteriaceae harbour a gene cluster called polyketide synthase (pks) island. This cluster is responsible for the synthesis of the genotoxin colibactin that might have an important role in the induction of double-strand DNA breaks, leading to promote human colorectal cancer (CRC). Eleven out of the eighty eight isolates (12.5%) were pks+, distributed as 7 (8%) isolates of E. coli, 2 (2.25%) of K. pneumoniae and 2 (2.25%) of E. aerogenes. The cytotoxic effects of selected pks+ isolates (E. coli and E. aerogenes) on HeLa cells were represented by decreasing cell numbers and enlarged cell nuclei in comparison to the untreated cells. Cytological changes were observed when the infected HeLa cells cultures were stained with AO/EBr and visualized under fluorescent microscope. Some changes that happened in the color of the nuclear chromatin were accompanied by DNA condensation and degradation and fragmentation of nuclei. HeLa cells with green unchanged nuclear chromatin were alive while those with orange-dark and bright red nuclei were dead. It was concluded that a proportion of the Entreobacteriaceae isolates from Iraqi patients was pks+, which exerted cytotoxic effects upon using them to kill HeLa cells. In this study the microscopic observation of the cell morphology reveals the cellular response to the genotoxic insult, with reduced numbers, striking giant cells phenotype (megalocytosis) and fragmentation of nuclei due to the cell cycle arrest and cellular senescenc

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Measurement of the VH,H → ττ process with the ATLAS detector at 13 TeV

A measurement of the Standard Model Higgs boson produced in association with a W or Z boson and decaying into a pair of τ-leptons is presented. This search is based on proton-proton collision data collected at √s = 13 TeV by the ATLAS experiment at the LHC corresponding to an integrated luminosity of 140 fb−1. For the Higgs boson candidate, only final states with at least one τ-lepton decaying hadronically (τ →hadrons + vτ ) are considered. For the vector bosons, only leptonic decay channels are considered: Z → ℓℓ and W → ℓvℓ, with ℓ = e, μ. An excess of events over the expected background is found with an observed (expected) significance of 4.2 (3.6) standard deviations, providing evidence of the Higgs boson produced in association with a vector boson and decaying into a pair of τ-leptons. The ratio of the measured cross-section to the Standard Model prediction is μττ VH = 1.28 +0.30 −0.29 (stat.) +0.25 −0.21 (syst.). This result represents the most accurate measurement of the VH(ττ) process achieved to date

Search for non-resonant Higgs boson pair production in final states with leptons, taus, and photons in pp collisions at √s = 13 TeV with the ATLAS detector

A search is presented for non-resonant Higgs boson pair production, targeting the bbZZ, 4V (V = W or Z), V V τ τ , 4τ , γγV V and γγτ τ decay channels. Events are categorised based on the multiplicity of light charged leptons (electrons or muons), hadronically decaying tau leptons, and photons. The search is based on a data sample of proton-proton collisions at √s = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 140 fb−1. No evidence of the signal is found and the observed (expected) upper limit on the cross-section for non-resonant Higgs boson pair production is determined to be 17 (11) times the Standard Model predicted cross-section at 95% confidence level under the background-only hypothesis. The observed (expected) constraints on the HHH coupling modifier, κλ, are determined to be −6.2 < κλ < 11.6 (−4.5 < κλ < 9.6) at 95% confidence level, assuming the Standard Model for the expected limits and that new physics would only affect κλ

Searches for exclusive Higgs boson decays into D⁎γ and Z boson decays into D0γ and Ks0γ in pp collisions at √s = 13 TeV with the ATLAS detector

Searches for exclusive decays of the Higgs boson into D⁎γ and of the Z boson into D0γ and Ks0γ can probe flavour-violating Higgs boson and Z boson couplings to light quarks. Searches for these decays are performed with a pp collision data sample corresponding to an integrated luminosity of 136.3 fb−1 collected at s=13TeV between 2016–2018 with the ATLAS detector at the CERN Large Hadron Collider. In the D⁎γ and D0γ channels, the observed (expected) 95% confidence-level upper limits on the respective branching fractions are B(H→D⁎γ)&lt;1.0(1.2)×10−3, B(Z→D0γ)&lt;4.0(3.4)×10−6, while the corresponding results in the Ks0γ channel are B(Z→Ks0γ)&lt;3.1(3.0)×10−6

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at √s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into diferent pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at √s = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, tt¯, and tb) or third-generation leptons (τν and τ τ ) are included in this kind of combination for the frst time. A simplifed model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confdence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Differential cross-sections for events with missing transverse momentum and jets measured with the ATLAS detector in 13 TeV proton-proton collisions

Measurements of inclusive, diferential cross-sections for the production of events with missing transverse momentum in association with jets in proton-proton collisions at √s = 13 TeV are presented. The measurements are made with the ATLAS detector using an integrated luminosity of 140 fb−1 and include measurements of dijet distributions in a region in which vector-boson fusion processes are enhanced. They are unfolded to correct for detector resolution and efficiency within the fiducial acceptance, and are designed to allow robust comparisons with a wide range of theoretical predictions. A measurement of differential cross sections for the Z → νν process is made. The measurements are generally well-described by Standard Model predictions except for the dijet invariant mass distribution. Auxiliary measurements of the hadronic system recoiling against isolated leptons, and photons, are also made in the same phase space. Ratios between the measured distributions are then derived, to take advantage of cancellations in modelling effects and some of the major systematic uncertainties. These measurements are sensitive to new phenomena, and provide a mechanism to easily set constraints on phenomenological models. To illustrate the robustness of the approach, these ratios are compared with two common Dark Matter models, where the constraints derived from the measurement are comparable to those set by dedicated detector-level searches

Measurement of vector boson production cross sections and their ratios using pp collisions at √s = 13.6 TeV with the ATLAS detector

Abstract available from publisher's website

Beam-induced backgrounds measured in the ATLAS detector during local gas injection into the LHC beam vacuum

Inelastic beam-gas collisions at the Large Hadron Collider (LHC), within a few hundred metres of the ATLAS experiment, are known to give the dominant contribution to beam backgrounds. These are monitored by ATLAS with a dedicated Beam Conditions Monitor (BCM) and with the rate of fake jets in the calorimeters. These two methods are complementary since the BCM probes backgrounds just around the beam pipe while fake jets are observed at radii of up to several metres. In order to quantify the correlation between the residual gas density in the LHC beam vacuum and the experimental backgrounds recorded by ATLAS, several dedicated tests were performed during LHC Run 2. Local pressure bumps, with a gas density several orders of magnitude higher than during normal operation, were introduced at different locations. The changes of beam-related backgrounds, seen in ATLAS, are correlated with the local pressure variation. In addition the rates of beam-gas events are estimated from the pressure measurements and pressure bump profiles obtained from calculations. Using these rates, the efficiency of the ATLAS beam background monitors to detect beam-gas events is derived as a function of distance from the interaction point. These efficiencies and characteristic distributions of fake jets from the beam backgrounds are found to be in good agreement with results of beam-gas simulations performed with theFluka Monte Carlo programme

Simultaneous energy and mass calibration of large-radius jets with the ATLAS detector using a deep neural network

The energy and mass measurements of jets are crucial tasks for the Large Hadron Collider experiments. This paper presents a new calibration method to simultaneously calibrate these quantities for large-radius jets measured with the ATLAS detector using a deep neural network (DNN). To address the specificities of the calibration problem, special loss functions and training procedures are employed, and a complex network architecture, which includes feature annotation and residual connection layers, is used. The DNN-based calibration is compared to the standard numerical approach in an extensive series of tests. The DNN approach is found to perform significantly better in almost all of the tests and over most of the relevant kinematic phase space. In particular, it consistently improves the energy and mass resolutions, with a 30% better energy resolution obtained for transverse momenta pT > 500 GeV