Search for Interstellar Water in the Translucent Molecular Cloud toward HD 154368

We report an upper limit of 9 x 10^{12} cm-2 on the column density of water in the translucent cloud along the line of sight toward HD 154368. This result is based upon a search for the C-X band of water near 1240 \AA carried out using the Goddard High Resolution Spectrograph of the Hubble Space Telescope. Our observational limit on the water abundance together with detailed chemical models of translucent clouds and previous measurements of OH along the line of sight constrain the branching ratio in the dissociative recombination of H_3O+ to form water. We find at the $3\sigma$ level that no more than 30% of dissociative recombinations of H_3O+ can lead to H_2O. The observed spectrum also yielded high-resolution observations of the Mg II doublet at 1239.9 \AA and 1240.4 \AA, allowing the velocity structure of the dominant ionization state of magnesium to be studied along the line of sight. The Mg II spectrum is consistent with GHRS observations at lower spectral resolution that were obtained previously but allow an additional velocity component to be identified.Comment: Accepted by ApJ, uses aasp

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

Forest as Stronghold of Local Ecological Practice: Currently Used Wild Food Plants in Polesia, Northern Ukraine

Local ecological practice (LEP, e.g., the everyday practice of collecting and using plants, including wild food plants) is shaped by nature (available local resources) and culture (local perceptions and knowledge on their usability), including a multitude of factors, among which language and geographical or cultural separation have been found to play crucial roles in affecting biocultural diversity. Also, proximity to the forest has been shown to increase the use of plants. We conducted ethnobotanical fieldwork within eastern and western regions of Ukrainian Polesia, during which we interviewed 118 people. Through semi-structured interviews, we recorded the distribution of the current uses of 70 wild food taxa. The analysis of use records revealed homogeneous distribution of use despite the geographical distance and different spoken dialects; however, we were able to single out the highly sylvan region of eastern Polesia as the area with highest biocultural diversity for the use of wild food plants. The results suggest that in the context of the overall homogenization of local ecological knowledge, the continued existence of unintended contact with nature through living and working in the forest may be the primary factor maintaining the broader LEP in the sylvan area of eastern Polesia. Місцева екологічна практика (MЕП, що включає повсякденну практику збору та використання дикорослих рослин у їжу) формується природою (місцевими ресурсами) та культурою (місцеві знання про їх використання), що включає безліч чинників, серед яких мова та географічне або культурне відокремлення відіграють вирішальну роль у впливі на біокультурне різноманіття. Також показано, що близькість до лісу збільшує використання рослин. Ми проводили етноботанічні польові роботи у двох областях Українського Полісся, в ході яких ми провели інтерв’ю з 118 людьми. За допомогою напівструктурованих інтерв’ю ми задокументували поточне використання 70 таксонів дикорослих рослин у їжу. Аналіз записів про вживання свідчить про однорідний розподіл використання, незважаючи на географічне розташування та різні розмовні діалекти; однак, ми змогли виділити лісистий регіон Східного Полісся як територію з найвищим біокультурним різноманіттям використання дикорослих рослин уїжу. Результати свідчать, що в контексті загальної гомогенізації місцевих екологічних знань, продовження існування контакту з природою живучи та працюючи в лісі може бути основним чинником, який підтримує ширшу MЕПу в лісовій зоні Східного Полісся

A random six-phase switch regulates pneumococcal virulence via global epigenetic changes

Streptococcus pneumoniae (the pneumococcus) is the world's foremost bacterial pathogen in both morbidity and mortality. Switching between phenotypic forms (or 'phases') that favour asymptomatic carriage or invasive disease was first reported in 1933. Here, we show that the underlying mechanism for such phase variation consists of genetic rearrangements in a Type I restriction-modification system (SpnD39III). The rearrangements generate six alternative specificities with distinct methylation patterns, as defined by single-molecule, real-time (SMRT) methylomics. The SpnD39III variants have distinct gene expression profiles. We demonstrate distinct virulence in experimental infection and in vivo selection for switching between SpnD39III variants. SpnD39III is ubiquitous in pneumococci, indicating an essential role in its biology. Future studies must recognize the potential for switching between these heretofore undetectable, differentiated pneumococcal subpopulations in vitro and in vivo. Similar systems exist in other bacterial genera, indicating the potential for broad exploitation of epigenetic gene regulation.Ana Sousa Manso, Melissa H. Chai, John M. Atack, Leonardo Furi, Megan De Ste Croix, Richard Haigh, Claudia Trappetti, Abiodun D. Ogunniyi, Lucy K. Shewell, Matthew Boitano, Tyson A. Clark, Jonas Korlach, Matthew Blades, Evgeny Mirkes, Alexander N. Gorban, James C. Paton, Michael P. Jennings, Marco R. Oggion

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras

Is DRE essential for the follow up of prostate cancer patients? A prospective audit of 194 patients

BACKGROUND: Prostate cancer follow up forms a substantial part of the urology outpatient workload. Nurse led prostate cancer follow up clinics are becoming more common. Routine follow-up may involve performing DRE, which may require training. OBJECTIVES: The aim of this audit was to assess the factors that influenced the change in the management of prostate cancer patients during follow up. This would allow us to pave the way towards a protocol driven follow up clinic led by nurse specialists without formal training in DRE. RESULTS: 194 prostate cancer patients were seen over a period of two months and all the patients had DRE performed on at least one occasion. The management was changed in 47 patients. The most common factor influencing this change was PSA trend. A change in DRE findings influenced advancement of the clinic visit in 2 patients. CONCLUSIONS: PSA is the most common factor influencing change in the management of these patients. Nurse specialists can run prostate cancer follow-up clinics in parallel to existing consultant clinics and reserve DRE only for those patients who have a PSA change or have onset of new symptoms. However larger studies are required involving all the subgroups of patients to identify the subgroups of patients who will require DRE routinely