Primary transcriptomes of Mycobacterium avium subsp. paratuberculosis reveal proprietary pathways in tissue and macrophages

<p>Abstract</p> <p>Background</p> <p><it>Mycobacterium avium </it>subsp. <it>paratuberculosis </it>(MAP) persistently infects intestines and mesenteric lymph nodes leading to a prolonged subclinical disease. The <it>MAP </it>genome sequence was published in 2005, yet its transcriptional organization in natural infection is unknown. While prior research analyzed regulated gene sets utilizing defined, in vitro stress related or advanced surgical methods with various animal species, we investigated the intracellular lifestyle of MAP in the intestines and lymph nodes to understand the MAP pathways that function to govern this persistence.</p> <p>Results</p> <p>Our transcriptional analysis shows that 21%, 8% and 3% of the entire MAP genome was represented either inside tissues, macrophages or both, respectively. Transcripts belonging to latency and cell envelope biogenesis were upregulated in the intestinal tissues whereas those belonging to intracellular trafficking and secretion were upregulated inside the macrophages. Transcriptomes of natural infection and in vitro macrophage infection shared genes involved in transcription and inorganic ion transport and metabolism. MAP specific genes within large sequence polymorphisms of ancestral <it>M. avium </it>complex were downregulated exclusively in natural infection.</p> <p>Conclusions</p> <p>We have unveiled common and unique MAP pathways associated with persistence, cell wall biogenesis and virulence in naturally infected cow intestines, lymph nodes and in vitro infected macrophages. This dichotomy also suggests that in vitro macrophage models may be insufficient in providing accurate information on the events that transpire during natural infection. This is the first report to examine the primary transcriptome of MAP at the local infection site (i.e. intestinal tissue). Regulatory pathways that govern the lifecycle of MAP appear to be specified by tissue and cell type. While tissues show a "shut-down" of major MAP metabolic genes, infected macrophages upregulate several MAP specific genes along with a putative pathogenicity island responsible for iron acquisition. Many of these regulatory pathways rely on the advanced interplay of host and pathogen and in order to decipher their message, an interactome must be established using a systems biology approach. Identified MAP pathways place current research into direct alignment in meeting the future challenge of creating a MAP-host interactome.</p

Genetic Diversity of Sapovirus in Children, Australia

Sapovirus was detected in 7 of 95 stool specimens from children with gastroenteritis of unknown etiology in Sydney, Australia, from August 2001 to August 2002 and from February 2004 to August 2004, by using reverse transcription–polymerase chain reaction. Sequence analysis of the N-terminal capsid region showed all human sapovirus genogroups

Sexual and drug use risk behaviour trajectories among people treated for recent HCV infection: the REACT study.

INTRODUCTION Exploration of sexual and drug use behaviours following treatment for recent hepatitis C virus (HCV) is limited. This analysis modelled behavioural trajectories following treatment for recent HCV and assessed reinfection. METHODS Participants treated for recent HCV in an international trial (enrolled 2017-2019) were followed at 3-monthly intervals for up to 2 years to assess longitudinal behaviours. Population-averaged changes were assessed using generalized estimating equations. Distinct behavioural trajectories were identified using group-based trajectory modelling. HCV reinfection incidence was calculated using person-years (PY) of observation. RESULTS During the follow-up of 212 participants (84% gay and bisexual men [GBM]; 69% HIV; 26% current injecting drug use [IDU]), behavioural trajectories for IDU and stimulant use (past month) did not change. However, population-averaged decreases in the likelihood of daily IDU (adjusted odds ratio [AOR] 0.83; 95% CI 0.72, 0.95) and opioid use (AOR 0.84; 95% CI 0.75, 0.93) were observed. Among GBM, behavioural trajectories for chemsex did not change. Population-averaged decreases in condomless anal intercourse with casual male partners (CAI-CMP) (AOR 0.95; 95% CI 0.90, 0.99) and group-sex (AOR 0.86; 95% CI 0.80, 0.93) were observed, but masked distinct trajectories. While a proportion had a decreased probability of CAI-CMP (23%) and group-sex (59%) post-treatment, a substantial proportion retained a high probability of these behaviours. High HCV reinfection incidence was observed for the sustained high probability IDU (33.0/100 PY; 95% CI 17.7, 61.3) and chemsex (23.3/100 PY; 95% CI 14.5, 37.5) trajectories. CONCLUSIONS Limited sexual and drug use behavioural change was observed following treatment for recent HCV, supporting access to surveillance and (re)treatment

Results of external quality assessment for proviral DNA testing of HIV tropism in the Maraviroc switch collaborative study

The Maraviroc Switch collaborative study (MARCH) is a study in aviremic patients on stable antiretroviral therapy and utilizes population-based sequencing of proviral DNA to determine HIV tropism and susceptibility to maraviroc. An external quality assessment (EQA) program was implemented to ensure competency in assessing the tropism of clinical samples conducted by MARCH laboratories (n = 14). The MARCH EQA has three prestudy phases assessing V3 loop sequencing and tropism determination using the bioinformatic algorithm geno2pheno, which generates a false-positive rate (FPR). DNA sequences with low FPRs are more likely to be from CXCR4-using (X4) viruses. Phase 1 of the EQA involved chromatogram interpretation. Phases 2, 2/3, and 3 involved patient and clonal samples. Clinical samples used in these phases were from treatment-experienced HIVinfected volunteers; 18/20 had viral loads o

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype

Search for new physics with dijet angular distributions in proton-proton collisions at root S = 13 TeV

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Search for supersymmetry in proton-proton collisions at 13 TeV using identified top quarks

A search for supersymmetry is presented based on proton-proton collision events containing identified hadronically decaying top quarks, no leptons, and an imbalance p(T)(miss) in transverse momentum. The data were collected with the CMS detector at the CERN LHC at a center-of-mass energy of 13 TeV, and correspond to an integrated luminosity of 35.9 fb(-1). Search regions are defined in terms of the multiplicity of bottom quark jet and top quark candidates, the p(T)(miss) , the scalar sum of jet transverse momenta, and themT2 mass variable. No statistically significant excess of events is observed relative to the expectation from the standard model. Lower limits on the masses of supersymmetric particles are determined at 95% confidence level in the context of simplified models with top quark production. For a model with direct top squark pair production followed by the decay of each top squark to a top quark and a neutralino, top squark masses up to 1020 GeVand neutralino masses up to 430 GeVare excluded. For amodel with pair production of gluinos followed by the decay of each gluino to a top quark-antiquark pair and a neutralino, gluino masses up to 2040 GeVand neutralino masses up to 1150 GeVare excluded. These limits extend previous results.Peer reviewe

Search for light bosons in decays of the 125 GeV Higgs boson in proton-proton collisions at root s=8 TeV

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Measurement of the top quark mass using single top quark events in proton-proton collisions at root s=8 TeV

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