The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest

The virulence of Mycobacterium tuberculosis depends on the ability of the bacilli to switch between replicative (growth) and non-replicative (dormancy) states in response to host immunity. However, the gene regulatory events associated with transition to dormancy are largely unknown. To address this question, we have assembled the largest M. tuberculosis transcriptional-regulatory network to date, and characterized the temporal response of this network during adaptation to stationary phase and hypoxia, using published microarray data. Distinct sets of transcriptional subnetworks (origons) were responsive at various stages of adaptation, showing a gradual progression of network response under both conditions. Most of the responsive origons were in common between the two conditions and may help define a general transcriptional signature of M. tuberculosis growth arrest. These results open the door for a systems-level understanding of transition to non-replicative persistence, a phenotypic state that prevents sterilization of infection by the host immune response and promotes the establishment of latent M. tuberculosis infection, a condition found in two billion people worldwide

Structural characterization of an all-aminosugar-containing capsular polysaccharide from Colwellia psychrerythraea 34H

Colwellia psychrerythraea strain 34H, a Gram-negative bacterium isolated from Arctic marine sediments, is considered a model to study the adaptation to cold environments. Recently, we demonstrated that C. psychrerythraea 34H produces two different extracellular polysaccharides, a capsular polysaccharide and a medium released polysaccharide, which confer cryoprotection to the bacterium. In this study, we report the structure of an additional capsular polysaccharide produced by Colwellia grown at a different temperature. The structure was determined using chemical methods, and one- and two-dimensional NMR spectroscopy. The results showed a trisaccharide repeating unit made up of only amino-sugar residues: N-acetyl-galactosamine, 2,4-diacetamido-2,4,6-trideoxy-glucose (bacillosamine), and 2-acetamido-2-deoxyglucuronic acid with the following structure: →4)-β-d-GlcpNAcA-(1 →3)-β-d-QuipNAc4NAc-(1 →3)-β-d-GalpNAc-(1 →. The 3D model, generated in accordance with 1H,1H-NOE NMR correlations and consisting of ten repeating units, shows a helical structure. In contrast with the other extracellular polysaccharides produced from Colwellia at 4 °C, this molecule displays only a low ice recrystallization inhibition activity

The proliferation marker Chromatin Assembly Factor-1 is of clinical value in predicting the biological behaviour of salivary gland tumours.

Salivary gland tumours (SGT) constitute a diagnostically challenging group of neoplasms with frequently unpredictable clinical outcome. The proliferation rate facilitates the identification of aggressive SGT. The Chromatin Assembly Factor-1 (CAF-1) is a major epigenetic regulator of nuclear chromatin organization during DNA replication. It plays a critical function in human tumourigenesis and has been proposed as a new proliferation and prognostic marker for some malignancies. This study focused on the role of CAF-1/p60 protein as a marker of clinical value for SGT. The expression of CAF-1/p60 was evaluated by immunohistochemistry on a retrospective series of 362 surgically excised benign and malignant SGT with different histogenesis and, when available, on fine-needle pre-surgical cytological biopsies. The resulting data were compared with traditional prognostic parameters, including the expression of the routine proliferation marker ki67/MIB1. CAF-1/p60 was detectable in all SGT, with highest degree of expression in metastasizing malignant tumours. Moreover, the cases of benign tumours which progressed to carcinoma during the follow-up, showed significantly higher CAF-1/p60 expression than non-progressing benign SGT, both on histological sections and cytological smears of the primary tumour. Cox's multiple regression analysis selected CAF-1/p60 expression as the best independent predictor of cancer development for benign SGT (p<0.0001), and the best independent predictor of metastasis onset for malignant tumours (p<0.0004). Overexpression of CAF-1/p60, on histological and/or cytological samples, characterizes malignant SGT with aggressive behaviour, irrespective of their specific histotype, and allows the early diagnosis of progression toward malignancy of morphologically benign tumours

Comparison of metabolic, oxidative and inflammatory status of Simmental × Holstein crossbred with parental breeds during the peripartal and early lactation periods.

AbstractThe aim of the research reported in this paper was to evaluate plasma concentrations of energy, oxidative and inflammatory biomarkers of Simmental (sire) × Holstein (dam) crossbred cows, in comparison with the two parental breeds during the peripartal and early lactation periods and to estimate the effects of heterosis for these traits. Thirty-three animals, managed under the same conditions, 8 Simmental (SI), 9 Holstein (HO) and 16 crossbred (CR) cows were enrolled in this study. Glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), total protein, albumin, creatinine and urea were determined in blood sampled at six different time points (30 ± 3 and 15 ± 3 d before the expected calving date, at calving and 15, 30 and 60 d after calving). Furthermore, derived reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), interleukin-6 (IL-6), haptoglobin (Hp) and serum amyloid A protein (SAA) were determined to evaluate inflammatory and oxidative status. Results showed that the CR group had significantly lower average values of glucose and NEFA when compared to HO group; signifcantly lower values of urea than SI group and significantly higher values of creatinine than HO. Furthermore, CR cows showed the lowest average value of d-ROMs with respect to SI and HO parental breeds. Finally, the average value of haptoglobin was significantly lower in CR and HO groups, when compared to SI group. As for the heterosis we found the highest (positive) percentage for CK (98%) and BAP (47%) and the lowest (negative) percentage for OSi (−75%) and d-ROMs (−39%). A negative percentage was also found for the glucose (−11%) and NEFA (−20%) toward the Simmental parental breed. Our results suggest a different response among the three genetic groups during the peripartal and early lactation periods. In particular, CR and SI cows seem more adaptable regarding energy metabolism and oxidative status. Heterosis led to a positive effect on those parameters in Simmental (sire) × Holstein (dam) crossbred cows F1 population (50% Simmental and 50% Holstein)

Immunodiagnosis of tuberculosis: new questions, new tools conference 2008

Human infection with Mycobacterium tuberculosis exists as a spectrum of conditions ranging from asymptomatic infection to active disease. Novel, accurate tuberculosis immunodiagnostics have been introduced over the last decade, but it remains challenging to timely diagnose active disease and to accurately distinguish asymptomatic M. tuberculosis infection from immune memory resulting from a prior infection eradicated by the host response. The conference titled Immunodiagnosis of Tuberculosis: New Questions, New Tools, which was held on September 21-23, 2008 in Virginia Beach, Virginia, United States, brought together basic scientists and clinical experts to discuss recent progress in tuberculosis research and diagnosis. Global analyses of M. tuberculosis biology and the host immune response, with emphasis on systems approaches to the study of host-pathogen interactions, were presented. Moreover, conference participants discussed new tests in the pipeline and reviewed new technologies leading to novel assay formats. The discussion included technologies ranging from simple, inexpensive point-of-care tests to automated molecular platforms for detection of multiple infections based on the “lab on a chip” concept. It was also recognized that the utility of any new diagnostic relies on laboratory capacity, accessibility, costs, and test deployment. The conference included lessons from the field. For example, the application of existing technologies to neglected areas, such as diagnosis in children and HIV+ populations, was discussed

Postoperative vacuum therapy following AMS™ LGX 700® inflatable penile prosthesis placement: penile dimension outcomes and overall satisfaction

Penile shortening after inflatable penile prosthesis for erectile dysfunction is a common postoperative patient complaint and can reduce overall satisfaction with the procedure. In this prospective study we report our results regarding penile dimensions and patient satisfaction outcomes after 1 year of follow-up from AMS™LGX700® penile prosthesis implant with 6 months of vacuum erectile device therapy. Seventy-four selected patients with medically refractory erectile dysfunction underwent AMS™ LGX 700® IPP placement. Postoperatively, patients were assigned vacuum device therapy for 5 min twice daily. Follow-up continued for 1 year after surgery. Dimensional and functional results were assessed. Baseline median preoperative stretched penile length and girth were 14 cm (range 10–17) and 9 cm (range 7–12), respectively. At the end of the study penile median dimensional outcomes were 17 cm (range 13–23) for length and 11 cm (range 10–13) for girth while a median number of 24 pumps (range 18–29) to fully inflate the device was seen. Baseline median International Index of Erectile Function (IIEF-5) score was 9 (range 5–11), at 6 months 20 (range 18–26) and at 1 year was 25 (range 20–27) (p &lt; 0.0001). Median Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score at the end of the follow-up was 74 (range 66–78). Our postoperative rehabilitation program is feasible and should be recommended after prothesis surgery in order to increase overall satisfaction with the procedure. Penile postoperative dimensional outcomes were statistically significant improved and complications were negligible

HST Survey of the Orion Nebula Cluster in the H₂O 1.4 μm Absorption Band. I. A Census of Substellar and Planetary-mass Objects

In order to obtain a complete census of the stellar and substellar population, down to a few M_(Jup) in the ~1 Myr old Orion Nebula Cluster, we used the infrared channel of the Wide Field Camera 3 of the Hubble Space Telescope with the F139M and F130N filters. These bandpasses correspond to the 1.4 μm H₂O absorption feature and an adjacent line-free continuum region. Out of 4504 detected sources, 3352 (about 75%) appear fainter than m₁₃₀ = 14 (Vega mag) in the F130N filter, a brightness corresponding to the hydrogen-burning limit mass M ≃ 0.072 M_⊙) at ~1 Myr. Of these, however, only 742 sources have a negative F130M–F139N color index, indicative of the presence of H₂O vapor in absorption, and can therefore be classified as bona fide M and L dwarfs, with effective temperatures T ≾ 2850 K at an assumed 1 Myr cluster age. On our color–magnitude diagram (CMD), this population of sources with H₂O absorption appears clearly distinct from the larger background population of highly reddened stars and galaxies with positive F130M–F139N color index and can be traced down to the sensitivity limit of our survey, m₁₃₀ ≃ 21.5, corresponding to a 1 Myr old ≃ 3 M_(Jup) planetary-mass object under about 2 mag of visual extinction. Theoretical models of the BT-Settl family predicting substellar isochrones of 1, 2, and 3 Myr down to ~1 M_(Jup) fail to reproduce the observed H₂O color index at M ≾ 20 M_(Jup). We perform a Bayesian analysis to determine extinction, mass, and effective temperature of each substellar member of our sample, together with its membership probability

Development of machine learning models for fractional flow reserve prediction in angiographically intermediate coronary lesions

Background: Fractional flow reserve (FFR) represents the gold standard in guiding the decision to proceed or not with coronary revascularization of angiographically intermediate coronary lesion (AICL). Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. Objectives: We sought to develop machine learning (ML) models based on clinical, angiographic and OCT variables for predicting FFR. Methods: Data from a multicenter, international, pooled analysis of individual patient's level data from published studies assessing FFR and OCT on the same target AICL were collected through a dedicated database to train (n = 351) and validate (n = 151) six two‐class supervised ML models employing 25 clinical, angiographic and OCT variables. Results: A total of 502 coronary lesions in 489 patients were included. The AUC of the six ML models ranged from 0.71 to 0.78, whereas the measured F1 score was from 0.70 to 0.75. The ML algorithms showed moderate sensitivity (range: 0.68–0.77) and specificity (range: 0.59–0.69) in detecting patients with a positive or negative FFR. In the sensitivity analysis, using 0.75 as FFR cut‐off, we found a higher AUC (0.78–0.86) and a similar F1 score (range: 0.63–0.76). Specifically, the six ML models showed a higher specificity (0.71–0.84), with a similar sensitivity (0.58–0.80) with respect to 0.80 cut‐off. Conclusions: ML algorithms derived from clinical, angiographic, and OCT parameters can identify patients with a positive or negative FFR