High-throughput, quantitative analyses of genetic interactions in E. coli.

Large-scale genetic interaction studies provide the basis for defining gene function and pathway architecture. Recent advances in the ability to generate double mutants en masse in Saccharomyces cerevisiae have dramatically accelerated the acquisition of genetic interaction information and the biological inferences that follow. Here we describe a method based on F factor-driven conjugation, which allows for high-throughput generation of double mutants in Escherichia coli. This method, termed genetic interaction analysis technology for E. coli (GIANT-coli), permits us to systematically generate and array double-mutant cells on solid media in high-density arrays. We show that colony size provides a robust and quantitative output of cellular fitness and that GIANT-coli can recapitulate known synthetic interactions and identify previously unidentified negative (synthetic sickness or lethality) and positive (suppressive or epistatic) relationships. Finally, we describe a complementary strategy for genome-wide suppressor-mutant identification. Together, these methods permit rapid, large-scale genetic interaction studies in E. coli

Key indicators to track current progress and future ambition of the Paris Agreement

Current emission pledges to the Paris Agreement appear insufficient to hold the global average temperature increase to well below 2 °C above pre-industrial levels. Yet, details are missing on how to track progress towards the â € Paris goal', inform the five-yearly â € global stocktake', and increase the ambition of Nationally Determined Contributions (NDCs). We develop a nested structure of key indicators to track progress through time. Global emissions track aggregated progress, country-level decompositions track emerging trends that link directly to NDCs, and technology diffusion indicates future reductions. We find the recent slowdown in global emissions growth is due to reduced growth in coal use since 2011, primarily in China and secondarily in the United States. The slowdown is projected to continue in 2016, with global CO 2 emissions from fossil fuels and industry similar to the 2015 level of 36 GtCO 2. Explosive and policy-driven growth in wind and solar has contributed to the global emissions slowdown, but has been less important than economic factors and energy efficiency. We show that many key indicators are currently broadly consistent with emission scenarios that keep temperatures below 2 °C, but the continued lack of large-scale carbon capture and storage threatens 2030 targets and the longer-term Paris ambition of net-zero emissions

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author

Twin Town in South Brazil: A Nazi's Experiment or a Genetic Founder Effect?

Cândido Godói (CG) is a small municipality in South Brazil with approximately 6,000 inhabitants. It is known as the “Twins' Town” due to its high rate of twin births. Recently it was claimed that such high frequency of twinning would be connected to experiments performed by the German Nazi doctor Joseph Mengele. It is known, however, that this town was founded by a small number of families and therefore a genetic founder effect may represent an alternatively explanation for the high twinning prevalence in CG. In this study, we tested specific predictions of the “Nazi's experiment” and of the “founder effect” hypotheses. We surveyed a total of 6,262 baptism records from 1959–2008 in CG catholic churches, and identified 91 twin pairs and one triplet. Contrary to the “Nazi's experiment hypothesis”, there is no spurt in twinning between the years (1964–1968) when Mengele allegedly was in CG (P = 0.482). Moreover, there is no temporal trend for a declining rate of twinning since the 1960s (P = 0.351), and no difference in twinning among CG districts considering two different periods: 1927–1958 and 1959–2008 (P = 0.638). On the other hand, the “founder effect hypothesis” is supported by an isonymy analysis that shows that women who gave birth to twins have a higher inbreeding coefficient when compared to women who never had twins (0.0148, 0.0081, respectively, P = 0.019). In summary, our results show no evidence for the “Nazi's experiment hypothesis” and strongly suggest that the “founder effect hypothesis” is a much more likely alternative for explaining the high prevalence of twinning in CG. If this hypothesis is correct, then this community represents a valuable population where genetic factors linked to twinning may be identified

The co-occurrence of autistic and ADHD dimensions in adults: an etiological study in 17 770 twins

Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) often occur together. To obtain more insight in potential causes for the co-occurrence, this study examined the genetic and environmental etiology of the association between specific ASD and ADHD disorder dimensions. Self-reported data on ASD dimensions social and communication difficulties (ASDsc), and repetitive and restricted behavior and interests (ASDr), and ADHD dimensions inattention (IA), and hyperactivity/impulsivity (HI) were assessed in a community sample of 17 770 adult Swedish twins. Phenotypic, genetic and environmental associations between disorder dimensions were examined in a multivariate model, accounting for sex differences. ASDr showed the strongest associations with IA and HI in both sexes (rp 0.33 to 0.40). ASDsc also correlated moderately with IA (females rp 0.29 and males rp 0.35) but only modestly with HI (females rp 0.17 and males rp 0.20). Genetic correlations ranged from 0.22 to 0.64 and were strongest between ASDr and IA and HI. Sex differences were virtually absent. The ASDr dimension (reflecting restricted, repetitive and stereotyped patterns of behavior, interests and activities) showed the strongest association with dimensions of ADHD, on a phenotypic, genetic and environmental level. This study opens new avenues for molecular genetic research. As our findings demonstrated that genetic overlap between disorders is dimension-specific, future gene-finding studies on psychiatric comorbidity should focus on carefully selected genetically related dimensions of disorders

Comparing different models of the development of verb inflection in early child Spanish

How children acquire knowledge of verb inflection is a long-standing question in language acquisition research. In the present study, we test the predictions of some current constructivist and generativist accounts of the development of verb inflection by focusing on data from two Spanish-speaking children between the ages of 2;0 and 2;6. The constructivist claim that children's early knowledge of verb inflection is only partially productive is tested by comparing the average number of different inflections per verb in matched samples of child and adult speech. The generativist claim that children's early use of verb inflection is essentially error-free is tested by investigating the rate at which the children made subjectverb agreement errors in different parts of the present tense paradigm. Our results show: 1) that, although even adults ' use of verb inflection in Spanish tends to look somewhat lexically restricted, both children's use of verb inflection was significantly less flexible than that of their caregivers, and 2) that, although the rate at which the two children produced subjectverb agreement errors in their speech was very low, this overall error rate hid a consistent pattern of error in which error rates were substantially higher in low frequency than in high frequency contexts, and substantially higher for low frequency than for high frequency verbs. These results undermine the claim that children's use of verb inflection is fully productive from the earliest observable stages, and are consistent with the constructivist claim that knowledge of verb inflection develops only gradually

Laparoscopic resection of a residual retroperitoneal tumor mass of nonseminomatous testicular germ cell tumors

Resection of a residual retroperitoneal tumor mass (RRRTM) is standard procedure after combination chemotherapy for metastatic nonseminomatous testicular germ cell tumors (NSTGCT). At the University Medical Center Groningen, 79 consecutive patients with disseminated NSTGCT were treated with cisplatin combination chemotherapy between 2005 and 2007. Laparoscopic RRRTM was performed for patients with RRTM located less than 5 cm ventrally or laterally from the aorta or the vena cava. The 29 patients who fulfilled the criteria had a median age of 25 years (range, 16-59 years). The stages of disease before chemotherapy treatment according to the Royal Marsden classification were 2A (n = 6, 21%), 2B (n = 14, 48%), 2C (n = 3, 10%), and 4 with a lymph node status of N2 (n = 6, 21%). The median duration of laparoscopy was 198 min (range, 122-325 min). The median diameter of the RRTM was 21 mm (range, 11-47 mm). Laparoscopic resection was successful for 25 patients (86%). Conversion was necessary for three patients (10%): two due to bleeding and one because of obesity. One nonplanned hand-assisted procedure (3%) also had to be performed. Histologic examination of the specimens showed fibrosis or necrosis in 12 patients (41%), mature teratoma in 16 patients (55%), and viable tumor in 1 patient (3%). The median hospital stay was 1 day (range, 1-6 days). During a median follow-up period of 47 months (29-70 months), one patient experienced an early relapse (1 month after the end of treatment) (4%). For properly selected patients, laparoscopic resection of RRTM is an improvement in the combined treatment of disseminated NSTGCT and associated with a short hospital stay, minimal morbidity, rapid recovery, and a neat cosmetic result. Long-term data to prove oncologic efficacy are awaited

Twinning across the Developing World

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