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Optimizing neonatal cardiovascular photo (magnet resonance/computed tomography).
Nicks are the most frequent form of DNA damage and a potential source of mutagenesis in human cells. By deep sequencing, we have identified factors and pathways that promote and limit mutagenic repair at a targeted nick in human cells. Mutations were distributed asymmetrically around the nick site. BRCA2 inhibited all categories of mutational events, including indels, SNVs and HDR. DNA2 and RPA promoted resection. DNA2 inhibited 1 bp deletions but contributed to longer deletions, as did REV7. POLQ stimulated SNVs. Parallel analysis of DSBs targeted to the same site identified similar roles for DNA2 and POLQ (but not REV7) in promoting deletions and for POLQ in stimulating SNVs. Insertions were infrequent at nicks, and most were 1 bp in length, as at DSBs. The translesion polymerase REV1 stimulated +1 insertions at one nick site but not another, illustrating the potential importance of sequence context in determining the outcome of mutagenic repair. These results highlight the potential for nicks to promote mutagenesis, especially in BRCA-deficient cells, and identify mutagenic signatures of DNA2, REV1, REV3, REV7 and POLQ.
Human African trypanosomiasis (HAT or sleeping sickness) is caused by the parasite Trypanosoma brucei sspp. The disease has two stages, a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system stage where the parasite penetrates the brain, causing death if untreated. Treatment is stage-specific, due to the blood-brain barrier, with less toxic drugs such as pentamidine used to treat stage 1. The objective of our research programme was to develop an intravenous formulation of pentamidine which increases CNS exposure by some 10-100 fold, leading to efficacy against a model of stage 2 HAT. This target candidate profile is in line with drugs for neglected diseases inititative recommendations.

To do this, we evaluated the physicochemical and structural characteristics of formulations of pentamidine with Pluronic micelles (triblock-copolymers of polyethylene-oxide and polypropylene oxide), selected candidates for efficacy and toxicity evaluation in vitro, quantified pvant to further developing block-copolymers as nanocarriers, improving BBB drug penetration and understanding the side effects of pentamidine.American trypanosomiasis, or Chagas disease, is transmitted by both domestic and sylvatic species of Triatominae which use sensory cues to locate their vertebrate hosts. Among them, odorants have been shown to play a key role. Previous work revealed morphological differences in the sensory apparatus of different species of Triatomines, but to date a comparative functional study of the olfactory system is lacking. After examining the antennal sensilla with scanning electronic microscopy (SEM), we compared olfactory responses of Rhodnius prolixus and the sylvatic Rhodnius brethesi using an electrophysiological approach. In electroantennogram (EAG) recordings, we first showed that the antenna of R. prolixus is highly responsive to carboxylic acids, compounds found in their habitat and the headspace of their vertebrate hosts. We then compared responses from olfactory sensory neurons (OSNs) housed in the grooved peg sensilla of both species, as these are tuned to these compounds using single-sensillum recordings (SSRs). In R. prolixus, the SSR responses revealed a narrower tuning breath than its sylvatic sibling, with the latter showing responses to a broader range of chemical classes. Additionally, we observed significant differences between these two species in their response to particular volatiles, such as amyl acetate and butyryl chloride. In summary, the closely related, but ecologically differentiated R. prolixus and R. brethesi display distinct differences in their olfactory functions. Considering the ongoing rapid destruction of the natural habitat of sylvatic species and the likely shift towards environments shaped by humans, we expect that our results will contribute to the design of efficient vector control strategies in the future.Adverse birth outcomes related to air pollution are well documented; however, few studies have accounted for infant sex. There is also scientific evidence that the neighborhood socioeconomic profile may modify this association even after adjusting for individual socioeconomic characteristics. BEZ235 The objective is to analyze the association between air pollution and birth weight by infant sex and neighborhood socioeconomic index. All birth weights (2008-2011) were geocoded at census block level. Each census block was assigned a socioeconomic deprivation level, as well as daily NO2 and PM10 concentrations. We performed a multilevel model with a multiple statistical test and sensible analysis using the spline function. Our findings suggest the existence of a differential association between air pollution and BW according to both neighborhood socioeconomic level and infant sex. However, due to multiple statistical tests and controlling the false discovery rate (FDR), all significant associations became either not statistically significant or borderline. Our findings reinforce the need for additional studies to investigate the role of the neighborhood socioeconomic which could differentially modify the air pollution effect.Understanding a species' historic range guides contemporary management and habitat restoration. Chinook salmon (Oncorhynchus tshawytscha) are an important commercial and recreational gamefish, but nine Chinook subspecies are federally threatened or endangered due to anthropogenic impacts. Several San Francisco Bay Area streams and rivers currently host spawning Chinook populations, but government agencies consider these non-native hatchery strays. Through the morphology-based analysis of 17,288 fish specimens excavated from Native American middens at Mission Santa Clara (CA-SCL-30H), Santa Clara County, circa 1781-1834 CE, 88 salmonid vertebrae were identified. Ancient DNA sequencing identified three separate individuals as Chinook salmon and the remainder as steelhead/rainbow trout (Oncorhynchus mykiss). These findings comprise the first physical evidence of the nativity of salmon to the Guadalupe River in San Jose, California, extending their documented historic range to include San Francisco Bay's southernmost tributary watershed.
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