Mutational Consequences of Ciprofloxacin in Escherichia coli

We examined the mutagenic specificity of the widely used antibiotic ciprofloxacin (CPR), which displays weak to moderate mutagenic activity in several bacteria and generates short in-frame deletions in rpoB in Staphylococcus aureus. To determine the spectrum of mutations in a system where any gene knockout would result in a recovered mutant, including frameshifts and both short and long deletions, we examined CPR-induced mutations in the thymidylate synthase-encoding thyA gene. Here, any mutation resulting in loss of thymidylate synthase activity generates trimethoprim (Trm) resistance. We found that deletions and insertions in all three reading frames predominated in the spectrum. They tend to be short deletions and cluster in two regions, one being a GC-rich region with potential extensive secondary structures. We also exploited the well-characterized rpoB-Rif(r) system in Escherichia coli to determine that cells grown in the presence of sublethal doses of CPR not only induced short in-frame deletions in rpoB, but also generated base substitution mutations resulting from induction of the SOS system. Some of the specific point mutations prominent in the spectrum of a strain that overproduces the dinB-encoded Pol IV were also present after growth in CPR. However, these mutations disappeared in CPR-treated dinB mutants, whereas the deletions remained. Moreover, CPR-induced deletions also occurred in a strain lacking all three SOS-induced polymerases. We discuss the implications of these findings for the consequences of overuse of CPR and other antibiotics

Mutational Consequences of Ciprofloxacin in Escherichia coli

We examined the mutagenic specificity of the widely used antibiotic ciprofloxacin (CPR), which displays weak to moderate mutagenic activity in several bacteria and generates short in-frame deletions in rpoB in Staphylococcus aureus To determine the spectrum of mutations in a system where any gene knockout would result in a recovered mutant, including frameshifts and both short and long deletions, we examined CPR-induced mutations in the thymidylate synthase-encoding thyA gene. Here, any mutation resulting in loss of thymidylate synthase activity generates trimethoprim (Trm) resistance. We found that deletions and insertions in all three reading frames predominated in the spectrum. They tend to be short deletions and cluster in two regions, one being a GC-rich region with potential extensive secondary structures. We also exploited the well-characterized rpoB-Rif(r) system in Escherichia coli to determine that cells grown in the presence of sublethal doses of CPR not only induced short in-frame deletions in rpoB, but also generated base substitution mutations resulting from induction of the SOS system. Some of the specific point mutations prominent in the spectrum of a strain that overproduces the dinB-encoded Pol IV were also present after growth in CPR. However, these mutations disappeared in CPR-treated dinB mutants, whereas the deletions remained. Moreover, CPR-induced deletions also occurred in a strain lacking all three SOS-induced polymerases. We discuss the implications of these findings for the consequences of overuse of CPR and other antibiotics

Community Perspectives on the Creation of a Hospital-Based Doula Program

Objective: Racial and ethnic inequities in perinatal health outcomes are pervasive. Doula support is an evidence-based practice for improving maternal outcomes. However, women in lower-income populations often do not have access to doulas. This study explored community perspectives on doula care to inform the development of a hospital-based doula program to serve primarily low-income women of color. Methods: Four focus groups and four individual interviews were conducted with: (1) women who were pregnant or parenting a child under age 2 (n=20); (2) people who had provided support during a birth in the previous 2 years (n=5); and (3) women who had received doula training (n=4). Results: Participants had generally positive perceptions of doula services. Many aspects of doula support desired by participants are core to birth doula services. Participants identified ways that doulas could potentially address critical gaps in health care services known to impact outcomes (e.g., continuity of care and advocacy), and provide much-needed support in the postpartum period. Responses also suggested that doula training and hospital-based doula programs may need to be adapted to address population-specific needs (e.g., women with substance use disorder and younger mothers). Novel program suggestions included “on call” informational doulas. Conclusions: Findings suggested that women in racial/ethnic minority and lower income groups may be likely to utilize a hospital-based doula program and identified adaptations to traditional doula care that may be required to best meet the needs of women in groups with higher risk of poor maternal health and birth outcomes

Archeointensity in Northeast Brazil over the past five centuries

This study presents the first archeointensity results from Northeast Brazil obtained from 14 groups of architectural brick fragments sampled in the city of Salvador, Bahia State (13 degrees S, 38.5 degrees W) and dated between the middle of the XVIth century and the beginning of the XIXth century. The dating is ascertained by historical documents complemented by archeological constraints, yielding in all cases age uncertainties of less than 50 years. Analyses were carried out using two experimental protocols: 1 the ""zero field-in field"" version of the classical Thellier and Thellier method as proposed by Coe (TT-ZI), including partial thermoremanent magnetization (pTRM) and pTRM-tail checks, and 2 the Triaxe procedure involving continuous high temperature magnetization measurements. Both TRM anisotropy and cooling rate effects were taken into account for the intensity determinations. The cooling rate effect was further explored for the TT-ZI protocol using three increasing slow cooling times (5 h, 10 h and 25 h) between 450 C and room temperature. Following archeological constraints, the slowest cooling time was retained in our study, yielding decreases of the raw intensity values by 4% to 14%. For each fragment, a mean intensity was computed and retained only when the data obtained from all specimens (between 2 and 6) satisfied a coherence test at similar to 5%. A total of 57 fragments (183 specimens) was considered for the computations of site-mean intensity values, with derived standard deviations of less than 8% of the corresponding means. When separately computed using the two experimental techniques, the site-mean intensity values always agree to within 5%. A good consistency is observed between intensity values of similar or close ages, which strengthen their reliability. Our data principally show a significant and continuous decrease in geomagnetic field intensity in Northeast Brazil between the first half of the XVIIth century and the XXth century. One result dated to the second half of the XVIth century further suggests that the geomagnetic field intensity reached a maximum around 1600 AD. This evolution is in good agreement with that expected in the city of Salvador from the available global geomagnetic field models. However, the accuracy of these models appears less well constrained between similar to 1550 AD and similar to 1650 AD. (C) 2010 Elsevier B.V. All rights reserved.FAPESP[2005/57782-4]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CAPES[3971/08-2]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)INSU-CNRSINSU-CNR

The Antibiotic Trimethoprim Displays Strong Mutagenic Synergy with 2-Aminopurine.

We show that trimethoprim (TMP), an antibiotic in current use, displays a strong synergistic effect on mutagenesis in Escherichia coli when paired with the base analog 2-aminopurine (2AP), resulting in a 35-fold increase in mutation frequencies in the rpoB-Rifr system. Combination therapies are often employed both as antibiotic treatments and in cancer chemotherapy. However, mutagenic effects of these combinations are rarely examined. An analysis of the mutational spectra of TMP, 2AP, and their combination indicates that together they trigger a response via an alteration in deoxynucleoside triphosphate (dNTP) ratios that neither compound alone can trigger. A similar, although less strong, response is seen with the frameshift mutagen ICR191 and 2AP. These results underscore the need for testing the effects on mutagenesis of combinations of antibiotics and chemotherapeutics

New historical archeointensity data from Brazil: Evidence for a large regional non-dipole field contribution over the past few centuries

We report new archeointensity data obtained from the analyses of baked clay elements (architectural and kiln brick fragments) sampled in Southeast Brazil and historically and/or archeologically dated between the end of the XVIth century and the beginning of the XXth century AD. The results were determined using the classical Thellier and Thellier protocol as modified by Coe, including partial thermoremanent magnetization (pTRM) and pTRM-tail checks, and the Triaxe protocol, which involves continuous high-temperature magnetization measurements. In both protocols, TRM anisotropy and cooling rate TRM dependence effects were taken into account for intensity determinations which were successfully performed for 150 specimens from 43 fragments, with a good agreement between intensity results obtained from the two procedures. Nine site-mean intensity values were derived from three to eight fragments and defined with standard deviations of less than 8%. The site-mean values vary from similar to 25 mu T to similar to 42 mu T and describe in Southeast Brazil a continuous decreasing trend by similar to 5 mu T per century between similar to 1600 AD and similar to 1900 AD. Their comparison with recent archeointensity results obtained from Northeast Brazil and reduced at a same latitude shows that: (1) the geocentric axial dipole approximation is not valid between these southeastern and northeastern regions of Brazil, whose latitudes differ by similar to 10 degrees, and (2) the available global geomagnetic field models (gufm1 models, their recalibrated versions and the CALSK3 models) are not sufficiently precise to reliably reproduce the non-dipole field effects which prevailed in Brazil for at least the 1600-1750 period. The large non-dipole contribution thus highlighted is most probably linked to the evolution of the South Atlantic Magnetic Anomaly (SAMA) during that period. Furthermore, although our dataset is limited, the Brazilian archeointensity data appear to support the view of a rather oscillatory behavior of the axial dipole moment during the past three centuries that would have been marked in particular by a moderate increase between the end of the XVIIIth century and the middle of the XIXth century followed by the well-known decrease from 1840 AD attested by direct measurements. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP[2005/57782-4]CAPES[3971/08-2]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)INSU-CNRSINSU-CNR

A single clonal lineage of transmissible cancer identified in two marine mussel species in South America and Europe

International audienceTransmissible cancers, in which cancer cells themselves act as an infectious agent, have been identified in Tasmanian devils, dogs, and four bivalves. We investigated a disseminated neoplasia affecting geographically distant populations of two species of mussels (Mytilus chilensis in South America and M. edulis in Europe). Sequencing alleles from four loci (two nuclear and two mitochondrial) provided evidence of transmissible cancer in both species. Phylogenetic analysis of cancer-associated alleles and analysis of diagnostic SNPs showed that cancers in both species likely arose in a third species of mussel (M. trossulus), but these cancer cells are independent from the previously identified transmissible cancer in M. trossulus from Canada. Unexpectedly, cancers from M. chilensis and M. edulis are nearly identical, showing that the same cancer lineage affects both. Thus, a single transmissible cancer lineage has crossed into two new host species and has been transferred across the Atlantic and Pacific Oceans and between the Northern and Southern hemispheres