4-[(Dimethyl­amino)methyl­idene]-2-(4-nitro­phen­yl)-1,3-oxazol-5(4H)-one

The title mol­ecule, C12H11N3O4, is essentially planar, the r.m.s. deviation for all non-H atoms being 0.068 Å. An intra­molecular C—H⋯N hydrogen bond occurs. The crystal packing is dominated by π–π inter­actions [shortest centroid–centroid distance = 3.6312 (16) Å], which lead to supra­molecular chains that are linked into a three-dimensional network via C—H⋯O contacts. The crystal was found to be a non-merohedral twin (twin law −1 0 0/0 −1 0/ 0.784 0 1), the fractional contribution of the minor component being approx­imately 22%

Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA

HIV-1-infected individuals harbor a latent reservoir of infected CD4⁺ T cells that is not eradicated by antiretroviral therapy (ART). This reservoir presents the greatest barrier to an HIV-1 cure and has remained difficult to characterize, in part, because the vast majority of integrated sequences are defective and incapable of reactivation. To characterize the replication-competent reservoir, we have combined two techniques, quantitative viral outgrowth and qualitative sequence analysis of clonal outgrowth viruses. Leukapheresis samples from four fully ART-suppressed, chronically infected individuals were assayed at two time points separated by a 4- to 6-mo interval. Overall, 54% of the viruses emerging from the latent reservoir showed gp160 env sequences that were identical to at least one other virus. Moreover, 43% of the env sequences from viruses emerging from the reservoir were part of identical groups at the two time points. Groups of identical expanded sequences made up 54% of proviral DNA, and, as might be expected, the sequences of replication-competent viruses in the active reservoir showed limited overlap with integrated proviral DNA, most of which is known to represent defective viruses. Finally, there was an inverse correlation between proviral DNA clone size and the probability of reactivation, suggesting that replication-competent viruses are less likely to be found among highly expanded provirus-containing cell clones

The Pine River Statement: Human Health Consequences of DDT Use

Objectives: Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction: We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis: Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions: Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDThttp://dx.doi.org/10.1289/ehp.1174

A voz dos bandos: colectivos de justiça e ritos da palavra portuguesa em Timor Leste colonial

Este artigo examina as relações entre o discurso da justiça e a prática do ritual nos bandos do governo colonial português em Timor Leste, entre a segunda metade do século XIX e as primeiras décadas do século XX. Os bandos consistiam em ordens e instruções de comando emanadas pelo governador português em Díli, e comunicadas de forma cerimonial por oficiais às populações dos diversos reinos timorenses dispersos pelo país. Bandos eram um instrumento por excelência de governação colonial dos assuntos indígenas, servindo para arbitrar conflitos, punir transgressões e, em geral, instituir realidades no mundo timorense. Contudo, esta instituição assumiu igualmente uma singular expressão nos usos timorenses, servindo bandos para comunicar também as ordens de autoridades tradicionais, os liurais. O artigo acompanha as variações coloniais e indígenas que os bandos adquiriram em Timor Leste, conceptualizando-os enquanto colectivos de justiça. Ao considerar assim os bandos como colectivos – formações heterogéneas em que elementos linguísticos e não linguísticos se combinam na produção de efeitos de poder sobre as populações – o artigo propõe uma via conceptual alternativa às perspectivas linguísticas e literárias de análise do discurso colonial

Investigating the role of the Est3 protein in yeast telomere replication

The Est3 subunit of yeast telomerase, which adopts a predicted OB-fold, is essential for telomere replication. To assess the possible contributions that Est3 might make to enzyme catalysis, we compared telomerase activity from wild type and est3-Δ strains of Saccharomyces castellii, which revealed that loss of the Est3 subunit results in a 2- to 3-fold decline in nucleotide addition. This effect was not primer-specific, based on assessment of a panel of primers that spanned the template of the S. castellii telomerase RNA. Furthermore, using nuclear magnetic resonance chemical shift perturbation, no chemical shift change was observed at any site in the protein upon addition of single-stranded DNA, arguing against a role for Est3 in recognition of telomeric substrates by telomerase. Addition of exogenous Est3 protein, including mutant Est3 proteins that are severely impaired for telomere replication in vivo, fully restored activity in est3-Δ telomerase reactions. Thus, Est3 performs an in vivo regulatory function in telomere replication, which is distinct from any potential contribution that Est3 might make to telomerase activity

Life satisfaction and risk of burnout among men and women working as physiotherapists

Objectives: Recently in Poland as a result of the high rate of aging population and high rates of morbidity, a growing demand for the physiotherapist profession is observed. The results of this study can be used to formulate principles for better organization of physiotherapist's workplace in order to prevent occurrence of burnout. The aim of this study is to investigate the effect of gender on satisfaction with life and burnout among active physiotherapists. Material and Methods: The survey was anonymous and voluntary, and involved a group of 200 active physiotherapists working in health care units and educational centers in Poland. The study group was selected randomly and incidentally. Each respondent received a demographic data sheet and a set of self-rating questionnaires (Life Satisfaction Questionnaire, Burnout Scale Inventory). Results: Burnout among men decreased along with increasing satisfaction with one's work and occupation, friends, relatives and acquaintances, sexuality, and increased due to greater satisfaction with one's housing status. Burnout among women decreased along with increasing satisfaction with one's health, free time and friends, relatives and acquaintances, and increased due to work at a setting other than a health care unit or educational center. Statistical analysis failed to reveal any significant differences with regard to the BSI domains and with regard to the overall burnout index as well as with regard to the assessment of satisfaction with life between female and male physiotherapists. Conclusions: Satisfaction with children, marriage and partnership, with one's work and occupation, interactions with friends, relatives and acquaintances and sexuality may contribute to reduction of burnout among men. Women who are satisfied with their children, family, health, free time and contacts with friends, relatives and acquaintances are less prone to burnout. Weak financial situation among women and deficiency of free time among men can induce burnout. Improving staff happiness may contribute to decreasing burnout

Fungal GH25 muramidases : New family members with applications in animal nutrition and a crystal structure at 0.78Å resolution

Muramidases/lysozymes hydrolyse the peptidoglycan component of the bacterial cell wall. They are found in many of the glycoside hydrolase (GH) families. Family GH25 contains muramidases/lysozymes, known as CH type lysozymes, as they were initially discovered in the Chalaropsis species of fungus. The characterized enzymes from GH25 exhibit both β-1,4-N-acetyl- and β-1,4-N,6-O-diacetylmuramidase activities, cleaving the β-1,4-glycosidic bond between N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) moieties in the carbohydrate backbone of bacterial peptidoglycan. Here, a set of fungal GH25 muramidases were identified from a sequence search, cloned and expressed and screened for their ability to digest bacterial peptidoglycan, to be used in a commercial application in chicken feed. The screen identified the enzyme from Acremonium alcalophilum JCM 736 as a suitable candidate for this purpose and its relevant biochemical and biophysical and properties are described. We report the crystal structure of the A. alcalophilum enzyme at atomic, 0.78 Å resolution, together with that of its homologue from Trichobolus zukalii at 1.4 Å, and compare these with the structures of homologues. GH25 enzymes offer a new solution in animal feed applications such as for processing bacterial debris in the animal gut

Large herbivores may alter vegetation structure of semi-arid savannas through soil nutrient mediation

In savannas, the tree–grass balance is governed by water, nutrients, fire and herbivory, and their interactions. We studied the hypothesis that herbivores indirectly affect vegetation structure by changing the availability of soil nutrients, which, in turn, alters the competition between trees and grasses. Nine abandoned livestock holding-pen areas (kraals), enriched by dung and urine, were contrasted with nearby control sites in a semi-arid savanna. About 40 years after abandonment, kraal sites still showed high soil concentrations of inorganic N, extractable P, K, Ca and Mg compared to controls. Kraals also had a high plant production potential and offered high quality forage. The intense grazing and high herbivore dung and urine deposition rates in kraals fit the accelerated nutrient cycling model described for fertile systems elsewhere. Data of a concurrent experiment also showed that bush-cleared patches resulted in an increase in impala dung deposition, probably because impala preferred open sites to avoid predation. Kraal sites had very low tree densities compared to control sites, thus the high impala dung deposition rates here may be in part driven by the open structure of kraal sites, which may explain the persistence of nutrients in kraals. Experiments indicated that tree seedlings were increasingly constrained when competing with grasses under fertile conditions, which might explain the low tree recruitment observed in kraals. In conclusion, large herbivores may indirectly keep existing nutrient hotspots such as abandoned kraals structurally open by maintaining a high local soil fertility, which, in turn, constrains woody recruitment in a negative feedback loop. The maintenance of nutrient hotspots such as abandoned kraals by herbivores contributes to the structural heterogeneity of nutrient-poor savanna vegetation

In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs

Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology