A Tool for Multiple Targeted Genome Deletions that Is Precise, Scar-Free, and Suitable for Automation.

Many advances in synthetic biology require the removal of a large number of genomic elements from a genome. Most existing deletion methods leave behind markers, and as there are a limited number of markers, such methods can only be applied a fixed number of times. Deletion methods that recycle markers generally are either imprecise (remove untargeted sequences), or leave scar sequences which can cause genome instability and rearrangements. No existing marker recycling method is automation-friendly. We have developed a novel openly available deletion tool that consists of: 1) a method for deleting genomic elements that can be repeatedly used without limit, is precise, scar-free, and suitable for automation; and 2) software to design the method's primers. Our tool is sequence agnostic and could be used to delete large numbers of coding sequences, promoter regions, transcription factor binding sites, terminators, etc in a single genome. We have validated our tool on the deletion of non-essential open reading frames (ORFs) from S. cerevisiae. The tool is applicable to arbitrary genomes, and we provide primer sequences for the deletion of: 90% of the ORFs from the S. cerevisiae genome, 88% of the ORFs from S. pombe genome, and 85% of the ORFs from the L. lactis genome

Maternal hemoglobin concentrations across pregnancy and maternal and child health: a systematic review and meta‐analysis

Maternal anemia is a well‐recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection for mother and child. We conducted a systematic review and meta‐analysis to examine the associations of maternal Hb concentrations with a range of maternal and infant health outcomes, accounting for the timing of measurement (preconception, and first, second, and third trimesters), etiology of anemia, and cutoff category. The systematic review included 272 studies and the meta‐analysis included 95 studies. Low maternal Hb (\u3c110 g/L) was associated with poor birth outcomes (low birth weight, preterm birth, small‐for‐gestational‐age (SGA), stillbirth, and perinatal and neonatal mortality) and adverse maternal outcomes (postpartum hemorrhage, preeclampsia, and blood transfusion). High maternal Hb (\u3e130 g/L) was associated with increased odds of SGA, stillbirth, preeclampsia, and gestational diabetes. Relationships varied by the timing of measurement and cutoff category (stronger associations with lower cutoffs); limited data were available on anemia etiology. There were insufficient data for other maternal outcomes and long‐term child health outcomes. Current data are insufficient for determining if revisions to current Hb cutoffs are required. Pooled high‐quality individual‐level data analyses, as well as prospective cohort studies, would be valuable to inform the reevaluation of Hb cutoffs

Phonetic variation and change in the Cockney Diaspora: The role of place, gender, and identity

Recent research has suggested that two linguistic processes are displacing Cockney: the emergence of Multicultural London English (MLE) in inner London and dialect levelling (e.g. Kerswill & Williams 2005). This study investigates firstly whether Cockney phonetic features have ‘moved East’ to Essex (Fox 2015), and secondly the features’ indexicality in relation to place and identity. Fifty-four participants from Debden, an outpost of the Cockney Diaspora, completed a sociolinguistic interview. Vowel measurements were made from a wordlist and passage, and quantitative attitudinal and qualitative data were extracted from a questionnaire and interviews. Overall, changes in identity as a result of social change exceeded linguistic changes, and linguistic labels were not interpreted uniformly across the community. Whilst Cockney variants were largely maintained in young speakers, they were transposed onto an ‘Essex’ accent. Furthermore, some young women but no young men considered themselves Cockney, likely due to the matrifocal nature of Cockney. (Cockney, phonetic variation and change, dialect levelling, identity, indexicality, gende

Composição química e atividade inibidora de acetilcolinesterase de óleos voláteis de Myrceugenia myrcioides(Cambess.) O. Berg and Eugenia riedeliana O. Berg, Myrtaceae

The chemical composition of volatile oils from two Myrtaceae species, Myrceugenia myrcioidesand Eugenia riedeliana, both native from the Brazilian Atlantic Rain Forest, was analyzed by GC-MS. Acetylcholinesterase inhibitory activity was colorimetrically evaluated for these oils. For M. myrcioides, monoterpene hydrocarbons represented the major class in the volatile oil, with α-pinene as the most abundant component and a weak inhibitory activity was observed, whilst for E. riedeliana sesquiterpenes were found in higher amounts, being valerianol the major compound, and this oil presented a strong acetylcholinesterase inhibition.A composição química dos óleos voláteis de duas espécies de Myrtaceae, Myrceugenia myrcioidese Eugenia riedeliana, ambas nativas da Mata Atlântica, foi analisada por CG-EM. A atividade inibidora de acetilcolinesterase foi determinada colorimetricamente para estes óleos. Em M. myrcioides, hidrocarbonetos monoterpênicos representaram a classe majoritária de compostos presentes no óleo volátil, sendo α-pineno o componente mais abundante e a atividade inibidora de acetilcolinesterase foi baixa, enquanto para E. riedelianaos sesquiterpenos foram observados em maiores concentrações, sendo o valerianol o componente majoritário, e este óleo apresentou uma forte atividade inibidora da enzima.BIOTA/FAPESPCNPqCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

The impact of the 18F(a,p)21Ne reaction on asymptotic giant branch nucleosynthesis

We present detailed models of low and intermediate-mass asymptotic giant branch (AGB) stars with and without the 18F(a,p)21Ne reaction included in the nuclear network, where the rate for this reaction has been recently experimentally evaluated for the first time. The lower and recommended measured rates for this reaction produce negligible changes to the stellar yields, whereas the upper limit of the rate affects the production of 19F and 21Ne. The stellar yields increase by ~50% to up to a factor of 4.5 for 19F, and by factors of ~2 to 9.6 for 21Ne. While the 18}F(a,p)21Ne reaction competes with 18O production, the extra protons released are captured by 18O to facilitate the 18O(p,a)15N(a,g)19F chain. The higher abundances of 19F obtained using the upper limit of the rate helps to match the [F/O] ratios observed in AGB stars, but only for large C/O ratios. Extra-mixing processes are proposed to help to solve this problem. Some evidence that the 18F(a,p)21Ne rate might be closer to its upper limit is provided by the fact that the higher calculated 21Ne/22Ne ratios in the He intershell provide an explanation for the Ne isotopic composition of silicon-carbide grains from AGB stars. This needs to be confirmed by future experiments of the 18F(a,p)21Ne reaction rate. The availability of accurate fluorine yields from AGB stars will be fundamental for interpreting observations of this element in carbon-enhanced metal-poor stars.Comment: 9 pages, accepted for publication in Ap

Short RNAs Are Transcribed from Repressed Polycomb Target Genes and Interact with Polycomb Repressive Complex-2

Polycomb proteins maintain cell identity by repressing the expression of developmental regulators specific for other cell types. Polycomb repressive complex-2 (PRC2) catalyzes trimethylation of histone H3 lysine-27 (H3K27me3). Although repressed, PRC2 targets are generally associated with the transcriptional initiation marker H3K4me3, but the significance of this remains unclear. Here, we identify a class of short RNAs, ~50–200 nucleotides in length, transcribed from the 5′ end of polycomb target genes in primary T cells and embryonic stem cells. Short RNA transcription is associated with RNA polymerase II and H3K4me3, occurs in the absence of mRNA transcription, and is independent of polycomb activity. Short RNAs form stem-loop structures resembling PRC2 binding sites in Xist, interact with PRC2 through SUZ12, cause gene repression in cis, and are depleted from polycomb target genes activated during cell differentiation. We propose that short RNAs play a role in the association of PRC2 with its target genes.National Institutes of Health (U.S.) (Grant HG002668)National Institutes of Health (U.S.) (Grant NS055923

Does patient-provider race/ethnicity concordance impact outcomes for adults with lupus?

Background: Health disparities exist among the 1.5 million Americans with lupus, with women of color bearing higher disease rates and burden. Complex reasons include genetics, comorbidities, and socioeconomics. These factors may lead to differences in health-related outcomes in lupus. Aim: To determine if patient-provider racial/ethnic concordance plays a role in outcomes for adults with lupus. Method: For this scoping review, the authors searched PubMed Medline and CINAHL using keywords and subject headings for lupus, race or ethnicity, and patient-health professional concordance. Results: Despite an intentionally broadened search of literature, the authors identified a lack of studies examining the topic. Conclusions: Certain factors may explain the results: a lack of scientists studying the phenomenon, a focus of funding on bench science, and a non-diverse U.S. healthcare provider workforce. Other factors may exist. Implications for practice, policy, and research are presented

A microphysiological system model of therapy for liver micrometastases

Metastasis accounts for almost 90% of cancer-associated mortality. The effectiveness of cancer therapeutics is limited by the protective microenvironment of the metastatic niche and consequently these disseminated tumors remain incurable. Metastatic disease progression continues to be poorly understood due to the lack of appropriate model systems. To address this gap in understanding, we propose an all-human microphysiological system that facilitates the investigation of cancer behavior in the liver metastatic niche. This existing LiverChip is a 3D-system modeling the hepatic niche; it incorporates a full complement of human parenchymal and non-parenchymal cells and effectively recapitulates micrometastases. Moreover, this system allows real-time monitoring of micrometastasis and assessment of human-specific signaling. It is being utilized to further our understanding of the efficacy of chemotherapeutics by examining the activity of established and novel agents on micrometastases under conditions replicating diurnal variations in hormones, nutrients and mild inflammatory states using programmable microdispensers. These inputs affect the cues that govern tumor cell responses. Three critical signaling groups are targeted: the glucose/insulin responses, the stress hormone cortisol and the gut microbiome in relation to inflammatory cues. Currently, the system sustains functioning hepatocytes for a minimum of 15 days; confirmed by monitoring hepatic function (urea, α-1-antitrypsin, fibrinogen, and cytochrome P450) and injury (AST and ALT). Breast cancer cell lines effectively integrate into the hepatic niche without detectable disruption to tissue, and preliminary evidence suggests growth attenuation amongst a subpopulation of breast cancer cells. xMAP technology combined with systems biology modeling are also employed to evaluate cellular crosstalk and illustrate communication networks in the early microenvironment of micrometastases. This model is anticipated to identify new therapeutic strategies for metastasis by elucidating the paracrine effects between the hepatic and metastatic cells, while concurrently evaluating agent efficacy for metastasis, metabolism and tolerability.National Institutes of Health (U.S.) (Grant 1UH2TR000496-01)United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039