Differential stability of DNA crossovers in solution mediated by divalent cations

The assembly of DNA duplexes into higher-order structures plays a major role in many vital cellular functions such as recombination, chromatin packaging and gene regulation. However, little is currently known about the molecular structure and stability of direct DNADNA interactions that are required for such functions. In nature, DNA helices minimize electrostatic repulsion between double helices in several ways. Within crystals, B-DNA forms either right-handed crossovers by groovebackbone interaction or left-handed crossovers by groovegroove juxtaposition. We evaluated the stability of such crossovers at various ionic concentrations using large-scale atomistic molecular dynamics simulations. Our results show that right-handed DNA crossovers are thermodynamically stable in solution in the presence of divalent cations. Attractive forces at short-range stabilize such crossover structures with inter-axial separation of helices less than 20 . Right-handed crossovers, however, dissociate swiftly in the presence of monovalent ions only. Surprisingly, left-handed crossovers, assembled by sequence-independent juxtaposition of the helices, appear unstable even at the highest concentration of Mg2+studied here. Our study provides new molecular insights into chiral association of DNA duplexes and highlights the unique role divalent cations play in differential stabilization of crossover structures. These results may serve as a rational basis to understand the role DNA crossovers play in biological processes

Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs)

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.Peer reviewe

Randomised positive control trial of NSAID and antimicrobial treatment for calf fever caused by pneumonia

One hundred and fifty-four preweaning calves were followed between May and October 2015. Calves were fitted with continuous monitoring temperature probes (TempVerified FeverTag), programmed so a flashing light emitting diode (LED) light was triggered following six hours of a sustained ear canal temperature of ≥39.7°C. A total of 83 calves (61.9 per cent) developed undifferentiated fever, with a presumptive diagnosis of pneumonia through exclusion of other calf diseases. Once fever was detected, calves were randomly allocated to treatment groups. Calves in group 1 (NSAID) received 2 mg/kg flunixin meglumine (Allevinix, Merial) for three consecutive days and group 2 (antimicrobial) received 6 mg/kg gamithromycin (Zactran, Merial). If fever persisted for 72 hours after the initial treatment, calves were given further treatment (group 1 received antimicrobial and group 2 received NSAID). Calves in group 1 (NSAID) were five times more likely (P=0.002) to require a second treatment (the antimicrobial) after 72 hours to resolve the fever compared with the need to give group 2 (antimicrobial) calves a second treatment (NSAID). This demonstrates the importance of ongoing monitoring and follow-up of calves with respiratory disease. However, of calves with fever in group 1 (NSAID), 25.7 per cent showed resolution following NSAID-only treatment with no detrimental effect on the development of repeated fever or daily live weight gain. This suggests that NSAID alone may be a useful first-line treatment, provided adequate attention is given to ongoing monitoring to identify those cases that require additional antimicrobial treatment

Polarization-dependence of anomalous scattering in brominated DNA and RNA molecules, and importance of crystal orientation in single- and multiple-wavelength anomalous diffraction phasing

In this paper the anisotropy of anomalous scattering at the Br K-absorption edge in brominated nucleotides is investigated, and it is shown that this effect can give rise to a marked directional dependence of the anomalous signal strength in X-ray diffraction data. This implies that choosing the correct orientation for crystals of such molecules can be a crucial determinant of success or failure when using single- and multiple-wavelength anomalous diffraction (SAD or MAD) methods to solve their structure. In particular, polarized absorption spectra on an oriented crystal of a brominated DNA molecule were measured, and were used to determine the orientation that yields a maximum anomalous signal in the diffraction data. Out of several SAD data sets, only those collected at or near that optimal orientation allowed interpretable electron density maps to be obtained. The findings of this study have implications for instrumental choices in experimental stations at synchrotron beamlines, as well as for the development of data collection strategy programs

Non-specific, agar medium-related peaks can result in false positive Mycoplasma alkalescens and Mycoplasma arginini identification by MALDI-TOF MS

MALDI-TOF MS is a fast and accurate tool to identify Mycoplasma species in liquid media. However, when trying to identify presumptive Mycoplasma bovis (M. bovis) colonies from solid medium (the "direct transfer method") a surprisingly high occurrence of M. arginini and M. alkalescens identification was observed. It was hypothesized that agar medium components are associated with false positive identification with Mycoplasma spp., as M. bovis colonies are very small and grow into the agar. The objective of this study was to determine whether complete modified pleuropneumonia-like organism (PPLO) agar (supplemented with horse serum, sodium pyruvate, technical yeast extract, ampicillin sodium salt and colistin) and the separate components, result in false identification as Mycoplasma spp. by MALDI-TOF MS. A total of 100 samples were examined, of which 33% of the modified PPLO agar spots were identified as M. alkalescens (16%) and M. arginini (17%)), albeit with relatively low score values ( < 1.85). No false identification of M. bovis was obtained. Several medium components (unsupplemented PPLO agar, horse serum and colistin) resulted in spectra with peaks showing close matches with peaks present in the M. alkalescens and M. arginini database spectra. This study shows that the direct transfer method should be interpreted with caution, and one should strive to pick as little as possible agar when sampling Mycoplasma-like colonies from solid medium containing PPLO agar, horse serum and/or colistin

Anticipation of Emerging Disease Mycoplasma bovis: Prevention and Control

Mycoplasma bovis is one of the pathogens, causes respiratory, reproductive, mastitis and arthritis disorders in cattle. Due to the economic impact of this disease, Mycoplasma bovis must be free on farms. There are no pathognomonic symptoms of Mycoplasma infection, so it needs laboratory confirmation to diagnose. Many countries have routinely examined M. bovis on cases of mastitis, arthritis, pneumonia and reproductive disorders. There was no cases of respiratory disorder in cattle related to M. bovis infection reported in Indonesia. The fact that, in many countries almost that cases related to the presence of M. bovis. The presence of M. bovis in Indonesia should be investigated, considering that Indonesia imports cattle from Australia and New Zealand that expose to M. bovis. This paper discusses the incidence of M. bovis infection in many countries including its economic impact, clinical symptoms, and method of diagnosis and control of disease to anticipate the emergence of this disease in Indonesia

Remerciements

Nous remercions les personnes suivantes qui ont bien voulu répondre à nos questions à la Bibliothèque publique d’information (Bpi) : P. Arbaizar A. Meyer M. Benhamou D. Reynier A.-M. Blanc C. Stra T. Cremel C. Timsit F. Figuière J.-L. Villard M. Melot au Centre de création industrielle (CCI) : J. Chapelle R. Guidot A. Guiheux M.-L. Jousset C. Eveno V. Hahn au Musée national d’art moderne (MNAM) : J.-H. Martin C. Lawless à la « Revue parlée » : B. Gautier C. Valentin M.-T. Angneroh à l’Espac..

The Directions of Public Administration Reform Due to Romania’s Integration in the European Union

From the formal point of view, in Romania there is an institutional framework that haslooked favourable for operation in at least satisfactory conditions for the authorities at the political level andat the level of public administration . In fact, things are different, and Romanians have to admit that thesignals from EU authorities made in the last few years are in compliance with the reality, namely: if the factthat we complied with the political criterion has been accepted, public administrations do not operateaccording to the standards established for adhesion. The faulty operation of public administration is obvious,well known: “Public administration has become uncontrollable in certain fields, and the political level doesnot know what decisions to make because it only listens and it is only interested in nothing else exceptfratricide fights or other image related matters. There is a lack of political culture in making decisions. Andthere is also the so called “psychological corruption” from the desire to keep the power with any price, youare absolutely opaque, closed and refuse to change the way you work, the way to make decisions

Burnout in the ICU : potential consequences for staff and patient well-being

Peer reviewedAuthor versio

A comparison of the predictions of a finite element model and multiscale model for a rough MEMS electrical contact

Rough surface contact is difficult to model effectively due to multiple scales of detail that need to be considered. This work presents the results of a multiscale rough surface contact model in comparison to a finite element based deterministic model for the electrical contact of a MEMS microswitch. The real area of contact and electrical contact resistance are predicted and compared as a function of normal load. The results show good quantitative and qualitative correlation between the two methods. As expected, the contact area increases nominally linearly with load, while the contact resistance decreases with load. It is notable though that the contact pressure is up to 16% higher than the hardness (2.8 times yield strength), and could be even higher for other surfaces