Cl- secretion by trachea of CFTR (+/-) and (-/-) fetal mouse.

The absence of pathologic changes in newborn cystic fibrosis (CF) lung suggests that the fetal CF lung is inflated with a normal volume of liquid and that Cl- is secreted through paths other than the cystic fibrosis transmembrane conductance regulator (CFTR)-associated Cl- channel. We studied liquid content of distal lung and transepithelial electrical potential difference (PD) of cultured cystic tracheal explants from 16 to 19 day gestation fetal mice of CFTR (+/-)(heterozygous) females that were mated with CFTR (-/-) "knockout" males. Distal lung water content was not affected by fetal genotype. Basal PDs were not different (CFTR (+/-), 8.6 mV, and CFTR (-/-), 9.1 mV), and PDs of both groups were inhibited by intraluminal injection of amiloride (10(-4) M) (-25%) and after addition of bumetanide (10(-4) M) to the bath (-40%). Terbutaline (3 x 10(-5) M) induced a similar increase in PD (about 65%) in both groups. Intraluminal injection of ionomycin (2 x 10(-5) and 5 x 10(-6) M) raised PD in both groups (CFTR (+/-) by 32 and 27% and CFTR (-/-) by 41 and 11%). All of the increase in PD induced by terbutaline and ionomycin was inhibited by bumetanide. The PD response to terbutaline was not attenuated by pretreatment with ionomycin or the Ca2+ chelator BAPTA (10(-4) M). Ionomycin or ATP, but not terbutaline, increased intracellular Ca2+ concentration of isolated cultured tracheal epithelial cells

Systematic review of wastewater surveillance of antimicrobial resistance in human populations

Objectives: We systematically reviewed studies using wastewater for AMR surveillance in human populations, to determine: (i) evidence of concordance between wastewater-human AMR prevalence estimates, and (ii) methodological approaches which optimised identifying such an association, and which could be recommended as standard. We used Lin’s concordance correlation coefficient (CCC) to quantify concordance between AMR prevalence estimates in wastewater and human compartments (where CCC = 1 reflects perfect concordance), and logistic regression to identify study features (e.g. sampling methods) associated with high agreement studies (defined as >70% of within-study wastewater-human AMR prevalence comparisons within ±10%). Results: Of 8,867 records and 441 full-text methods reviewed, 33 studies were included. AMR prevalence data was extractable from 24 studies conducting phenotypic-only (n = 7), genotypic-only (n = 1) or combined (n = 16) AMR detection. Overall concordance of wastewater-human AMR prevalence estimates was reasonably high for both phenotypic (CCC = 0.85 [95% CI 0.8–0.89]) and genotypic approaches (CCC = 0.88 (95% CI 0.84–0.9)) despite diverse study designs, bacterial species investigated and phenotypic/genotypic targets. No significant relationships between methodological approaches and high agreement studies were identified using logistic regression; however, this was limited by inconsistent reporting of study features, significant heterogeneity in approaches and limited sample size. Based on a secondary, descriptive synthesis, studies conducting composite sampling of wastewater influent, longitudinal sampling >12 months, and time-/location-matched sampling of wastewater and human compartments generally had higher agreement. Conclusion: Wastewater-based surveillance of AMR appears promising, with high overall concordance between wastewater and human AMR prevalence estimates in studies irrespective of heterogenous approaches. However, our review suggests future work would benefit from: time-/location-matched sampling of wastewater and human populations, composite sampling of influent, and sampling >12 months for longitudinal studies. Further research and clear and consistent reporting of study methods is required to identify optimal practice

Metatranscriptomics analysis reveals a novel transcriptional and translational landscape during Middle East respiratory syndrome coronavirus infection

Among all RNA viruses, coronavirus RNA transcription is the most complex and involves a process termed “discontinuous transcription” that results in the production of a set of 3′-nested, co-terminal genomic and subgenomic RNAs during infection. While the expression of the classic canonical set of subgenomic RNAs depends on the recognition of a 6- to 7-nt transcription regulatory core sequence (TRS), here, we use deep sequence and metagenomics analysis strategies and show that the coronavirus transcriptome is even more vast and more complex than previously appreciated and involves the production of leader-containing transcripts that have canonical and noncanonical leader-body junctions. Moreover, by ribosome protection and proteomics analyses, we show that both positive- and negative-sense transcripts are translationally active. The data support the hypothesis that the coronavirus proteome is much vaster than previously noted in the literature

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

Mapping disparities in education across low- and middle-income countries

Educational attainment is an important social determinant of maternal, newborn, and child health1–3. As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting4–6. The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness7,8; however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health9–11. Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but—to our knowledge—no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries12–14. By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations

Search for long-lived doubly charged Higgs bosons in p(p)over-bar collisions at root s=1.96 TeV

We present a search for long-lived doubly charged Higgs bosons (H+/-+/-), with signatures of high ionization energy loss and muonlike penetration. We use 292 pb(-1) of data collected in p (p) over bar collisions at root s=1.96 TeV by the CDF II detector at the Fermilab Tevatron. Observing no evidence of long-lived doubly charged particle production, we exclude H-L(+/-+/-) and H-R(+/-+/-) bosons with masses below 133 GeV/c(2) and 109 GeV/c(2), respectively. In the degenerate case we exclude H+/-+/- mass below 146 GeV/c(2). All limits are quoted at the 95% confidence level

Measurement of the W+W- Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Dilepton Events

We present a measurement of the W+W- production cross section using 184/pb of ppbar collisions at a center-of-mass energy of 1.96 TeV collected with the Collider Detector at Fermilab. Using the dilepton decay channel W+W- -> l+l-vvbar, where the charged leptons can be either electrons or muons, we find 17 candidate events compared to an expected background of 5.0+2.2-0.8 events. The resulting W+W- production cross section measurement of sigma(ppbar -> W+W-) = 14.6 +5.8 -5.1 (stat) +1.8 -3.0 (syst) +-0.9 (lum) pb agrees well with the Standard Model expectation.Comment: 8 pages, 2 figures, 2 tables. To be submitted to Physical Review Letter