Browsing by Issue Date, starting with "2013-01"
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- Increased Survival of Antibiotic-Resistant Escherichia coli inside MacrophagesPublication . Miskinyte, M.; Gordo, I.Mutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in the rpoB, rpsL, and gyrA genes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits-growth rate and survival ability-of 12 Escherichia coli K-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, all E. coli streptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival of E. coli in the context of an infection.
- JAABA: interactive machine learning for automatic annotation of animal behaviorPublication . Kabra, Mayank; Robie, Alice A; Rivera-Alba, Marta; Branson, Steven; Branson, KristinWe present a machine learning-based system for automatically computing interpretable, quantitative measures of animal behavior. Through our interactive system, users encode their intuition about behavior by annotating a small set of video frames. These manual labels are converted into classifiers that can automatically annotate behaviors in screen-scale data sets. Our general-purpose system can create a variety of accurate individual and social behavior classifiers for different organisms, including mice and adult and larval Drosophila.
- THE OPPORTUNITY FOR BALANCING SELECTION IN EXPERIMENTAL POPULATIONS OFCAENORHABDITIS ELEGANSPublication . Chelo, Ivo M.; Teotónio, HenriqueThe role of balancing selection in maintaining diversity during the evolution of sexual populations to novel environments is poorly understood. To address this issue, we studied the impact of two mating systems, androdioecy and dioecy, on genotype distributions during the experimental evolution of Caenorhabditis elegans. We analyzed the temporal trajectories of 334 single nucleotide polymorphisms, covering 1/3 of the genome, and found extensive allele frequency changes and little loss of heterozygosities after 100 generations. As modeled with numerical simulations, SNP differentiation was consistent with genetic drift and average fitness effects of 2%, assuming that selection acted independently at each locus. Remarkably, inbreeding by self-fertilization was of little consequence to SNP differentiation. Modeling selection on deleterious recessive alleles suggests that the initial evolutionary dynamics can be explained by associative overdominance, but not the later stages because much lower heterozygosities would be maintained during experimental evolution. By contrast, models with selection on true overdominant loci can explain the heterozygote excess observed at all periods, particularly when negative epistasis or independent fitness effects were considered. Overall, these findings indicate that selection at single loci, including purging of recessive alleles, underlies most of the genetic differentiation accomplished during the experiment. Nonetheless, they also imply that maintenance of genetic diversity may in large part be due to balancing selection at multiple loci.
- Reductionism at the vertebrate kinetochorePublication . Stankovic, A.; Jansen, L. E. T.The kinetochore forms the site of attachment for mitotic spindle microtubules driving chromosome segregation. The interdependent protein interactions in this large structure have made it difficult to dissect the function of its components. In this issue, Hori et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201210106) present a novel and powerful methodology to address the sufficiency of individual proteins for the creation of a functional de novo centromere.
- Expression-based and co-localization detection of arabinogalactan protein 6 and arabinogalactan protein 11 interactors in Arabidopsis pollen and pollen tubesPublication . Costa, Mário; Nobre, Margarida Sofia; Becker, Jörg D; Masiero, Simona; Amorim, Maria Isabel; Pereira, Luís Gustavo; Coimbra, SílviaArabinogalactan proteins (AGPs) are cell wall proteoglycans that have been shown to be important for pollen development. An Arabidopsis double null mutant for two pollen-specific AGPs (agp6 agp11) showed reduced pollen tube growth and compromised response to germination cues in vivo. A microarray experiment was performed on agp6 agp11 pollen tubes to search for genetic interactions in the context of pollen tube growth. A yeast two-hybrid experiment for AGP6 and AGP11 was also designed.
- Telomerase Is Required for Zebrafish LifespanPublication . Henriques, Catarina M.; Carneiro, Madalena C.; Tenente, Inês M.; Jacinto, António; Ferreira, Miguel GodinhoTelomerase activity is restricted in humans. Consequentially, telomeres shorten in most cells throughout our lives. Telomere dysfunction in vertebrates has been primarily studied in inbred mice strains with very long telomeres that fail to deplete telomeric repeats during their lifetime. It is, therefore, unclear how telomere shortening regulates tissue homeostasis in vertebrates with naturally short telomeres. Zebrafish have restricted telomerase expression and human-like telomere length. Here we show that first-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopaenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescent cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is rescued in tp53(-/-)tert(-/-) mutants, underscoring p53 as mediator of telomerase deficiency and consequent telomere instability. Thus, telomerase is limiting for zebrafish lifespan, enabling the study of telomere shortening in naturally ageing individuals.
- Disengaging the Smc3/kleisin interface releases cohesin from Drosophila chromosomes during interphase and mitosisPublication . Eichinger, Christian S; Kurze, Alexander; Oliveira, Raquel A; Nasmyth, KimCohesin's Smc1, Smc3, and kleisin subunits create a tripartite ring within which sister DNAs are entrapped. Evidence suggests that DNA enters through a gate created by transient dissociation of the Smc1/3 interface. Release at the onset of anaphase is triggered by proteolytic cleavage of kleisin. Less well understood is the mechanism of release at other stages of the cell cycle, in particular during prophase when most cohesin dissociates from chromosome arms in a process dependent on the regulatory subunit Wapl. We show here that Wapl-dependent release from salivary gland polytene chromosomes during interphase and from neuroblast chromosome arms during prophase is blocked by translational fusion of Smc3's C-terminus to kleisin's N-terminus. Our findings imply that proteolysis-independent release of cohesin from chromatin is mediated by Wapl-dependent escape of DNAs through a gate created by transient dissociation of the Smc3/kleisin interface. Thus, cohesin's DNA entry and exit gates are distinct.