Genska karakterizacija, kloniranje i ekspresija Toll-like receptora 1 mRNA nilske tilapije (Oreochromis niloticus)

Toll-like receptors (TLRs) are the most studied group of pathogen recognition receptor categories that detects infectious agents in vertebrates. Fish TLRs exhibit clear, distinct features, structure and a larger diversity than in other vertebrates. This study focused on identifying and detecting the structure of Oreochromis niloticus (Nile tilapia) Toll- like receptor-1 (TLR1|) as a model in freshwater bony fish. The full-length cDNA sequence of Oreochromis niloticus TLR1 mRNA was cloned. Cloning and sequence analysis revealed that the complete cDNA sequence of Oreochromis niloticus TLR1 consists of 2355 base pairs and encodes a polypeptide of 785 amino acids. The molecular analysis of the amino acid sequence indicated that Oreochromis niloticus TLR1 has the standard structural features and major components of amino acids of TLR family members, and is considered an orthologue to the vertebrate TLR1, not a paralogue. The translated amino acid analysis showed 96%, 88%, 85%, and 85% degrees of identity with Zebra Mbuna, Sea bass, Damsel fish, and Clownfish, respectively; and showed 66% identity t with electric eels and 61% with starlets. Phylogenetic analysis revealed that the Nile tilapia TLR1 is closely related to Larimichthys crocea, Epinephelus coioides, and Takifugu rubripes TLR1. Oreochromis niloticus TLR1 was expressed in the kidneys, brain, spleen, intestines, muscle, liver, gills, heart and skin. Quantitative RT-PCR showed differences in the expression levels between the tested tissues. In conclusion, this study is the first report (according to our knowledge) and provides a complete molecular and functional characterization of Oreochromis niloticus toll-like receptor 1, which is considered to be functionally orthologous to TLR1 in other species models.Toll-like receptori (TLR) najviše su istraživana skupina receptora za prepoznavanje uzročnika bolesti u kralježnjaka. TLR u riba pokazuju jasna razlikovna svojstva, strukturu i veliku raznolikost u odnosu na druge kralježnjake. Ovo je istraživanje usredotočeno na identifikaciju i otkrivanje Toll-like receptora 1 (TLR1) u nilske tilapije (Oreochromis niloticus) kao predstavnika slatkovodnih riba. Klonirana je puna sekvencija cDNA TLR1 mRNA. Utvrđeno je da se kompletna sekvencija cDNA TLR1 nilske tilapije sastoji od 2355 baznih parova i kodira polipeptid od 785 aminokiselina. Molekularna analiza sekvencija aminokiselina upućuje na to da TLR1 nilske tilapije ima standardna strukturna svojstva i glavne komponente porodice TLR receptora i smatra se ortologom, ne paralogom TLR1 kralježnjaka. Analiza prevedenih aminokiselina pokazala je stupanj identičnost od 96 % s mbuna zebrom, 88 % s lubinom, 85 % s damsel ribom i 85 % s ribom klaun, dok je stupanj identičnosti s električnom jeguljom bio 66 %, a s ribom starlet 61 %. Filogenetska analiza pokazala je da je TLR1 nilske tilapije usko povezan s TLR1 vrsta Larimichthys crocea, Epinephelus coioides i Takifugu rubripes. TLR1 nilske tilapije bio je izražen u bubrezima, mozgu, slezeni, crijevima, mišiću, jetri, škrgama, srcu i na koži. Kvantitativni RT-PCR pokazao je razlike u razini ekspresije među testiranim tkivima. Prema našim podacima ovo je istraživanje prvo koje donosi kompletnu molekularnu i funkcionalnu karakterizaciju Toll-like receptora 1 nilske tilapije, te se smatra funkcionalnim ortologom TLR1 u drugih vrsta

In Vivo Investigation of the Ameliorating Effect of Copper Albumin Complex on chondroitin sulfate in Monosodium iodoacetate -Induced Knee Osteoarthritis

Osteoarthritis (OA) is a condition that manifests as cartilage deterioration and subchondral bone sclerosis in the joint tissues. The weight-bearing joint is most severely impacted by OA. According to some research, consuming foods high in copper albumin complex (cu-albumin complex) can help with OA-related joint degeneration and pain relief. The current study's objective to determine how oral administration of the cu-albumin complex as an anti-inflammatory medication affected the development of rat knee osteoarthritis (KOA). Fifty adult albino rats were divided into three groups: negative control untreated (n= 10, no KOA induction); positive untreated control (n= 20, KOA induction); and treated group (n= 20, KOA induction with administration of cu-albumin complex). According to the severity of the clinical symptoms, treated and untreated arthritic groups were equally divided into mild and severe groups (n=10). Monosodium iodoacetate (MIA) was used as intra-articular injection for osteoarthritis induction. Rats were euthanized after a month of the beginning of the experiment, and the joints were examined histopathologically and immunohistochemically. It was indicated that the treatment was effective in reducing KOA severity and in improvement of chondroitin sulfate of the affected cartilages. In conclusion, the structure of the chondroitin sulphate in the knee joint cartilages of KOA-affected rats was modified by the cu-albumin complex

Investigation of the Ameliorating Effect of Copper Albumin Complex on Lysyl oxidase in monosodium iodoacetate -Induced Knee Osteoarthritis in Rats

Knee osteoarthritis (KOA) is a common type of joint degeneration which causes progressive damage of the joint structure and has less therapeutic options. It has been found that oral consumption of Copper Albumin Complex as anti-inflammatory drug has a positive effect on the treatment of joint deterioration. The present study aimed to investigate the effect of oral administration of Copper Albumin Complex (cu-albumin complex) on Lysyl oxidase (LOX) which acts as a protective factor in KOA. Fifty adult albino rats were divided into 3 groups: negative control (10 normal rats); positive control (20 rats with KOA which left without induction treatment); and treated group (20 rats with KOA which treated with administration of copper albumin complex). Treated and untreated arthritic groups were subdivided equally into mild and severe groups (10 rats for each) according to the severity of clinical signs. KOA was induced by intra-articular injection of monosodium iodoacetate (MIA). At the experimental end, the joints were examined histopathologically and immunohistochemically after cervical dislocation of rats. It was observed that the treatment with CU- was effective in reducing disease severity and in improvement of Lysyl oxidase KOA. It was concluded that Copper albumin complex has a positive effect in the improvement of LOX of Knee joint cartilages of rats affected by osteoarthritis (OA)

Prognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications

COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients. 2022, The Author(s).The authors would like to thank all the patients, volunteers, and the healthcare co-workers from Allergy and Immunology Section-HMC, and Dr. Mohamed G.H. Mohamedali, Mr. Hassen Maatoug, and Mr. Ahmed Soliman from Hezm Mebairek General Hospital-HMC for developing disposable racks for samples transportation, tubes labeling, blood collection, and handling. We thank the support provided by Qatar University Biomedical Research Centre, Biosafety Level 3, and Associate Professor Hadi M. Yassine (M.Sc., Ph.D.). We also acknowledge the help of the Anti-Doping Lab-Qatar (ADLQ) and Qatar Red Crescent (QRC) for recruiting control samples. This work was supported by a grant fund from Hamad Medical Corporation (fund number MRC-05-003) and core funding from Qatar Biomedical Research Institute (QBRI).Scopu

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe