The contribution of transcriptomic and proteomic analysis in elucidating stress adaptation responses of Listeria monocytogenes

The foodborne transmission of Listeria monocytogenes requires physiological adaptation to various conditions, including the cold, osmotic, heat, acid, alkaline, and oxidative stresses, associated with food hygiene, processing, and preservation measures. We review the current knowledge on the molecular stress adaptation responses in L. monocytogenes cells as revealed through transcriptome, proteome, genetic, and physiological analysis. The adaptation of L. monocytogenes to stress exposure is achieved through global expression changes in a large number of cellular components. In addition, the cross-protection of L. monocytogenes exposed to different stress environments might be conferred through various cellular machineries that seem to be commonly activated by the different stresses. To assist in designing L. monocytogenes mitigation strategies for ready-to-eat food products, further experiments are warranted to specifically evaluate the effects of food composition, additives, preservatives, and processing technologies on the modulation of L. monocytogenes cellular components in response to specific stresses

Predictability of Muscle Fiber Characteristics using the Biodex System 3

Nannapaneni, N., Schmidt, G. (FACSM), Cox, M., Boutote, R., William Paterson University, Wayne, NJ. Purpose: The purpose of this study was to examine whether the isokinetic dynamometer is capable of distinguishing muscle fiber characteristics between men and women. Methods: 14 participants (7 men and 7 women) of various fitness levels volunteered for this study. Isokinetic testing was conducted using the BIODEX System 3 dynamometer. Each participant was secured in the chair; seat height was adjusted; knee alignment was set at the lateral joint line adjacent to the dynamometer. Power Test: Participants performed 5 sets of 1 maximal voluntary contraction (MVC) repetition with a 30 sec rest period between sets at 60°/sec. Fatigue Test: Participants performed 1 set of 50 (MVC) repetitions at 180°/sec. Prior to this test there was a 2 minute rest period. Results: There were significant differences between men and women for Power and Peak Torque. When comparing the fatigue test results, men showed a greater decrease in peak torque and at a faster time to fatigue compared to women from their first 25 repetitions to their final 25 repetitions. Conclusions: The results of this study demonstrated that men fatigue faster and at an increased rate compared to women. The results of the tests were inconclusive in determining muscle fiber composition. This study did provide valuable data in regards to quadriceps muscle characteristic differences amongst. In the power test, the male subjects on average produced greater peak torque values in their quadriceps. The males produced peak torque values that were approximately 150% greater than those produced by their female counterparts. These differences can be attributed to the fact that males on average have greater muscle mass than females

The Role of Dietary Vitamin E in Experimental Listeria monocytogenes Infections in Turkeys

The current study was designed to determine if dietary vitamin E influenced either the gut clearance or levels of peripheral blood CD4+ and CD8+ T lymphocytes in adult turkeys experimentally infected with Listeria monocytogenes. Turkeys were fed vitamin E (0, 100, or 200 IU) from day of hatch to time of necropsy. After 6 wk on the experimental diet, turkeys were orally inoculated with L. monocytogenes (∼ 109 cfu). To monitor infection status, cloacal swabs were taken on selected days post-inoculation (DPI). At necropsy, samples of viscera, including liver, spleen, cecum, duodenum, ileum, and colon were collected and cultured for L. monocytogenes. In experiments 1 and 2, recovery of L. monocytogenes from cloacal swabs, tissues, and intestines from turkeys fed vitamin E was generally lower than that from turkeys fed the control diet, although these differences were not statistically significant. When data from both trials were combined, L. monocytogenes was cultured less frequently from cloacal swabs of the vitamin E-treated group (200 IU) on 2 and 3 DPI, when compared to controls (0 IU, P \u3c 0.01). There were no changes in virulence characteristics of L. monocytogenes cells, as measured by in vitro killing of Ped-2E9 cells, recovered from cloacal swabs or tissues of experimentally infected turkeys fed the control or a vitamin E treatment diet. Flow cytometric analysis indicated that CD4+ and CD8+ peripheral blood T lymphocytes were elevated at 6 and 8 DPI in infected turkeys given 200 IU vitamin E

The Prevalence of L. monocytogenes in Cull Sows

The goal of this study was to determine the distribution of Listeria monocytogenes in cull sows and their pork. Two trials were conducted at a single packing plant in 2001 (n=179 cull sows) and in 2002 (n= 160 cull sows). Fecal samples collected antemortem (trial 1) as well as animal tissues, carcass, and environmental swabs, and meat block samples collected at the abattoir (trials 1 and 2) were analyzed. When results from both trials were combined, overall L. monocytogenes was detected in five or 0.17% of the total samples (n=2,858). Specifically, L. monocytogenes was confirmed in a tonsil sample (0.55% of tonsils positive) and in a carcass swab sample (0.56% of carcasses) before the organic acid rinse. L. monocytogenes was recovered in three (1.21%) meat block samples (n=213). These data indicate that L. monocytogenes is present in the cull sow and their pork

Antitumor Activity of 2,9-Di-\u3cem\u3eSec\u3c/em\u3e-Butyl-1,10-Phenanthroline

The anti-tumor effect of a chelating phen-based ligand 2,9-di-sec-butyl-1,10-phenanthroline (dsBPT) and its combination with cisplatin were examined in both lung and head and neck cancer cell lines and xenograft animal models in this study. The effects of this agent on cell cycle and apoptosis were investigated. Protein markers relevant to these mechanisms were also assessed. We found that the inhibitory effect of dsBPT on lung and head and neck cancer cell growth (IC50 ranged between 0.1–0.2 μM) was 10 times greater than that on normal epithelial cells. dsBPT alone induced autophagy, G1 cell cycle arrest, and apoptosis. Our in vivo studies indicated that dsBPT inhibited tumor growth in a dose-dependent manner in a head and neck cancer xenograft mouse model. The combination of dsBPT with cisplatin synergistically inhibited cancer cell growth with a combination index of 0.3. Moreover, the combination significantly reduced tumor volume as compared with the untreated control (p = 0.0017) in a head and neck cancer xenograft model. No organ related toxicities were observed in treated animals. Our data suggest that dsBPT is a novel and potent antitumor drug that warrants further preclinical and clinical development either as a single agent or in combination with known chemotherapy drugs such as cisplatin

Multi Agent System for Machine Learning Under Uncertainty in Cyber Physical Manufacturing System

Recent advancement in predictive machine learning has led to its application in various use cases in manufacturing. Most research focused on maximising predictive accuracy without addressing the uncertainty associated with it. While accuracy is important, focusing primarily on it poses an overfitting danger, exposing manufacturers to risk, ultimately hindering the adoption of these techniques. In this paper, we determine the sources of uncertainty in machine learning and establish the success criteria of a machine learning system to function well under uncertainty in a cyber-physical manufacturing system (CPMS) scenario. Then, we propose a multi-agent system architecture which leverages probabilistic machine learning as a means of achieving such criteria. We propose possible scenarios for which our architecture is useful and discuss future work. Experimentally, we implement Bayesian Neural Networks for multi-tasks classification on a public dataset for the real-time condition monitoring of a hydraulic system and demonstrate the usefulness of the system by evaluating the probability of a prediction being accurate given its uncertainty. We deploy these models using our proposed agent-based framework and integrate web visualisation to demonstrate its real-time feasibility

Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth

Systemic delivery of siRNA to solid tumors remains challenging. In this study, we investigated the systemic delivery of a siRNA nanoparticle targeting ribonucleotide reductase subunit M2 (RRM2), and evaluated its intratumoral kinetics, efficacy and mechanism of action. Knockdown of RRM2 by an RNAi mechanism strongly inhibited cell growth in head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cell lines. In a mouse xenograft model of HNSCC, a single intravenous injection led to the accumulation of intact nanoparticles in the tumor that disassembled over a period of at least 3 days, leading to target gene knockdown lasting at least 10 days. A four-dose schedule of siRNA nanoparticle delivering RRM2 siRNA targeted to HNSCC tumors significantly reduced tumor progression by suppressing cell proliferation and inducing apoptosis. These results show promise for the use of RRM2 siRNA-based therapy for HNSCC and possibly NSCLC

Prognostic biomarkers in patients with human immunodeficiency virusâ positive disease with head and neck squamous cell carcinoma

BackgroundWe examined the prognostic value of a panel of biomarkers in patients with squamous cell carcinoma of the head and neck (SCCHN) who were human immunodeficiency virus (HIV) positive (HIVâ positive head and neck cancer) and HIV negative (HIVâ negative head and neck cancer).MethodsTissue microarrays (TMAs) were constructed using tumors from 41 disease siteâ matched and ageâ matched HIVâ positive head and neck cancer cases and 44 HIVâ negative head and neck cancer controls. Expression of tumor biomarkers was assessed by immunohistochemistry (IHC) and correlations examined with clinical variables.ResultsExpression levels of the studied oncogenic and inflammatory tumor biomarkers were not differentially regulated by HIV status. Among patients with HIVâ positive head and neck cancer, laryngeal disease site (P = .003) and Clavienâ Dindo classification IV (CD4) counts <200 cells/μL (P = .01) were associated with poor prognosis. Multivariate analysis showed that p16 positivity was associated with improved overall survival (OS; P < .001) whereas increased expression of transforming growth factorâ beta (TGFâ β) was associated with poor clinical outcome (P = .001).ConclusionDisease site has significant effect on the expression of biomarkers. Expression of tumor TGFâ β could be a valuable addition to the conventional risk stratification equation for improving head and neck cancer disease management strategies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139994/1/hed24911.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139994/2/hed24911_am.pd

Rationale and design of The Delphi Trial – I(RCT)(2): international randomized clinical trial of rheumatoid craniocervical treatment, an intervention-prognostic trial comparing 'early' surgery with conservative treatment [ISRCTN65076841]

BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease, which affects 1% of the population. Hands and feet are most commonly involved followed by the cervical spine. The spinal column consists of vertebrae stabilized by an intricate network of ligaments. Especially in the upper cervical spine, rheumatoid arthritis can cause degeneration of these ligaments, causing laxity, instability and subluxation of the vertebral bodies. Subsequent compression of the spinal cord and medulla oblongata can cause severe neurological deficits and even sudden death. Once neurological deficits occur, progression is inevitable although the rapidity of progression is highly variable. The first signs and symptoms are pain at the back of the head caused by compression of the major occipital nerve, followed by loss of strength of arms and legs. The severity of the subluxation can be observed with radiological investigations (MRI, CT) with a high sensitivity. The authors have sent a Delphi Questionnaire about the current treatment strategies of craniocervical involvement by rheumatoid arthritis to an international forum of expert rheumatologists and surgeons. The timing of surgery in patients with radiographic instability without evidence of neurological deficit is an area of considerable controversy. If signs and symptoms of myelopathy are present there is little chance of recovery to normal levels after surgery. DESIGN: In this international multicenter randomized clinical trial, early surgical atlantoaxial fixation in patients with rheumatoid arthritis and radiological abnormalities without neurological deficits will be compared with prolonged conservative treatment. The main research question is whether early surgery can prevent radiological and neurological progression. A cost-effectivity analysis will be performed. 250 patients are needed to answer the research question. DISCUSSION: Early surgery could prevent serious neurological deficits, but may have peri-operative morbidity and loss of rotation of the head and neck. The objective of this study is to identify the best timing of surgery for patients at risk for the development of neurological signs and symptoms

Somatic Mutagenesis with a Sleeping Beauty Transposon System Leads to Solid Tumor Formation in Zebrafish

Large-scale sequencing of human cancer genomes and mouse transposon-induced tumors has identified a vast number of genes mutated in different cancers. One of the outstanding challenges in this field is to determine which genes, when mutated, contribute to cellular transformation and tumor progression. To identify new and conserved genes that drive tumorigenesis we have developed a novel cancer model in a distantly related vertebrate species, the zebrafish, Danio rerio. The Sleeping Beauty (SB) T2/Onc transposon system was adapted for somatic mutagenesis in zebrafish. The carp ß-actin promoter was cloned into T2/Onc to create T2/OncZ. Two transgenic zebrafish lines that contain large concatemers of T2/OncZ were isolated by injection of linear DNA into the zebrafish embryo. The T2/OncZ transposons were mobilized throughout the zebrafish genome from the transgene array by injecting SB11 transposase RNA at the 1-cell stage. Alternatively, the T2/OncZ zebrafish were crossed to a transgenic line that constitutively expresses SB11 transposase. T2/OncZ transposon integration sites were cloned by ligation-mediated PCR and sequenced on a Genome Analyzer II. Between 700–6800 unique integration events in individual fish were mapped to the zebrafish genome. The data show that introduction of transposase by transgene expression or RNA injection results in an even distribution of transposon re-integration events across the zebrafish genome. SB11 mRNA injection resulted in neoplasms in 10% of adult fish at ∼10 months of age. T2/OncZ-induced zebrafish tumors contain many mutated genes in common with human and mouse cancer genes. These analyses validate our mutagenesis approach and provide additional support for the involvement of these genes in human cancers. The zebrafish T2/OncZ cancer model will be useful for identifying novel and conserved genetic drivers of human cancers