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in pay and working conditions. - The horse and buggy reached its _____ in the early 1900s with the production of the automobile. - In order to entice the consumer,
companies will offer a short-term _____ on payments for buying merchandise. - I loved studying _____ because I enjoyed looking at interesting rocks and how they came to be on
Earth. - The young teen's heroic effort to save the family from the sinking car was _____. - The spy's disguise and _____ actions were undetected by foreign government officials.
- The haying season is my favorite part of _____ life. Add your own comment - Kindergarten Sight Words List - The Five Warning Signs of Asperger's Syndrome - What
Makes a School Effective? - Child Development Theories - Why is Play Important? Social and Emotional Development, Physical Development, Creative Development - 10 Fun Activities for Children with Autism -
- Provides access to the research & evidence base informing teacher education. The Children's Plan: Building Brighter Futures - DCSF website dedicated to the Children's Plan, includes key documents, case studies and implications for professionals, parents, and young people. Better Behaviour - Better Learning - Includes useful introductions and resources for a range of whole school approaches including Solution Oriented
Country-specific antibiotic use practices impact the human gut resistome. Forslund, K., Sunagawa, S., Roat Kultima, J., Mende, D., Arumugam, M., Typas, A. & Bork, P. Genome Res. 2013 Apr 8.
Despite increasing concerns over inappropriate use of antibiotics in medicine and food production, population-level resistance transfer into the human gut microbiota has not been demonstrated beyond individual case studies. To
determine the "antibiotic resistance potential" for entire microbial communities, we employ metagenomic data and quantify the totality of known resistance genes in each community (its resistome) for 68 classes and
subclasses of antibiotics. In 252 fecal metagenomes from three countries, we show that the most abundant resistance determinants are those for antibiotics also used in animals, and for antibiotics that
have been available longer. Resistance genes are also more abundant in samples from Spain, Italy and France than from Denmark, the US, or Japan. Where comparable country-level data on antibiotic
use in both humans and animals are available, differences in these statistics match the observed resistance potential differences. The results are robust over time as the antibiotic resistance determinants of
individuals persist in the human gut flora for at least a year. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Typas, A., Banzhaf, M., Gross, C.A. &
Vollmer, W. Nat Rev Microbiol. 2012 Feb;10(2):123-36. doi: 10.1038/nrmicro2677. How bacteria grow and divide while retaining a defined shape is a fundamental question in microbiology, but technological advances are now
driving a new understanding of how the shape-maintaining bacterial peptidoglycan sacculus grows. In this Review, we highlight the relationship between peptidoglycan synthesis complexes and cytoskeletal elements, as well as recent
evidence that peptidoglycan growth is regulated from outside the sacculus in Gram-negative bacteria. We also discuss how growth of the sacculus is sensitive to mechanical force and nutritional status, and
describe the roles of peptidoglycan hydrolases in generating cell shape and of D-amino acids in sacculus remodelling. Selective ribosome profiling reveals the cotranslational chaperone action of trigger factor in vivo.
Oh, E., Becker, A.H., Sandikci, A., Huber, D., Chaba, R., Gloge, F., Nichols, R.J., Typas, A., Gross, C.A., Kramer, G., Weissman, J.S. & Bukau, B. Cell. 2011 Dec 9;147(6):1295-308. As
nascent polypeptides exit ribosomes, they are engaged by a series of processing, targeting, and folding factors. Here, we present a selective ribosome profiling strategy that enables global monitoring of when
these factors engage polypeptides in the complex cellular environment. Studies of the Escherichia coli chaperone trigger factor (TF) reveal that, though TF can interact with many polypeptides, beta-barrel outer-membrane proteins
are the most prominent substrates. Loss of TF leads to broad outer-membrane defects and premature, cotranslational protein translocation. Whereas in vitro studies suggested that TF is prebound to ribosomes waiting
for polypeptides to emerge from the exit channel, we find that in vivo TF engages ribosomes only after approximately 100 amino acids are translated. Moreover, excess TF interferes with cotranslational
removal of the N-terminal formyl methionine. Our studies support a triaging model in which proper protein biogenesis relies on the fine-tuned, sequential engagement of processing, targeting, and folding factors. PAPERCLIP:
Escherichia coli sigma senses sequence and conformation of the promoter spacer region. Singh, S.S., Typas, A., Hengge, R. & Grainger, D.C. Nucleic Acids Res. 2011 Jul;39(12):5109-18. Epub 2011 Mar 11.
In bacteria, promoter identification by RNA polymerase is mediated by a dissociable sigma factor. The housekeeping sigma(70) factor of Escherichia coli recognizes two well characterized DNA sequence elements, known as
the '-10' and '-35' hexamers. These elements are separated by 'spacer' DNA, the sequence of which is generally considered unimportant. Here, we use a combination of bioinformatics, genetics and biochemistry
to show that sigma(70) can sense the sequence and conformation of the promoter spacer region. Our data illustrate how alterations in spacer region sequence can increase promoter activity. This stimulatory
effect requires sigma(70) side chain R451, which is located in close proximity to the non-template strand at promoter position -18. Conversely, R451 is not required to mediate transcriptional stimulation by
improvement of the -10 element. Mutation of sigma(70) residue R451, which is highly conserved, results in reduced growth rate, consistent with a central role in promoter recognition. Phenotypic landscape of
a bacterial cell. Nichols, R.J., Sen, S., Choo, Y.J., Beltrao, P., Zietek, M., Chaba, R., Lee, S., Kazmierczak, K.M., Lee, K.J., Wong, A., Shales, M., Lovett, S., Winkler, M.E., Krogan,
N.J., Typas, A. & Gross, C.A. Cell. 2011 Jan 7;144(1):143-56. Epub 2010 Dec 23. The explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with
phenotypes imperative. Using E. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. Probing growth
profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover leads for gene function and drug action,
and understand higher-order organization of the bacterial chromosome. We highlight new information derived from the study, including insights into a gene involved in multiple antibiotic resistance and the synergy between
high-confidence associations between hundreds of annotated and uncharacterized genes as well as inferences about the mode of action of several poorly understood drugs. Regulation of peptidoglycan synthesis by outer-membrane proteins.
Typas, A., Banzhaf, M., van den Berg van Saparoea, B., Verheul, J., Biboy, J., Nichols, R.J., Zietek, M., Beilharz, K., Kannenberg, K., von Rechenberg, M., Breukink, E., den Blaauwen, T.,
Gross, C.A. & Vollmer, W. Cell. 2010 Dec 23;143(7):1097-109. Growth of the mesh-like peptidoglycan (PG) sacculus located between the bacterial inner and outer membranes (OM) is tightly regulated to ensure
cellular integrity, maintain cell shape, and orchestrate division. Cytoskeletal elements direct placement and activity of PG synthases from inside the cell, but precise spatiotemporal control over this process is poorly
understood. We demonstrate that PG synthases are also controlled from outside of the sacculus. Two OM lipoproteins, LpoA and LpoB, are essential for the function, respectively, of PBP1A and PBP1B,
the major E. coli bifunctional PG synthases. Each Lpo protein binds specifically to its cognate PBP and stimulates its transpeptidase activity, thereby facilitating attachment of new PG to the sacculus.
LpoB shows partial septal localization, and our data suggest that the LpoB-PBP1B complex contributes to OM constriction during cell division. LpoA/LpoB and their PBP-docking regions are restricted to gamma-proteobacteria, providing
models for niche-specific regulation of sacculus growth. High-throughput, quantitative analyses of genetic interactions in E. coli. Typas, A., Nichols, R.J., Siegele, D.A., Shales, M., Collins, S.R., Lim, B., Braberg, H.,
Yamamoto, N., Takeuchi, R., Wanner, B.L., Mori, H., Weissman, J.S., Krogan, N.J. & Gross, C.A. Nat Methods. 2008 Sep;5(9):781-7. 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. Stationary phase reorganisation of the Escherichia coli transcription machinery by Crl protein,
a fine-tuner of sigmas activity and levels. Typas, A., Barembruch, C., Possling, A. & Hengge, R. EMBO J. 2007 Mar 21;26(6):1569-78. Epub 2007 Mar 1. Upon environmental changes, bacteria reschedule
gene expression by directing alternative sigma factors to core RNA polymerase (RNAP). This sigma factor switch is achieved by regulating relative amounts of alternative sigmas and by decreasing the competitiveness
of the dominant housekeeping sigma(70). Here we report that during stationary phase, the unorthodox Crl regulator supports a specific sigma factor, sigma(S) (RpoS), in its competition with sigma(70) for core
RNAP by increasing the formation of sigma(S)-containing RNAP holoenzyme, Esigma(S). Consistently, Crl has a global regulatory effect in stationary phase gene expression exclusively through sigma(S), that is, on sigma(S)-dependent genes
only. Not a specific promoter motif, but sigma(S) availability determines the ability of Crl to exert its function, rendering it of major importance at low sigma(S) levels. By promoting the
formation of Esigma(S), Crl also affects partitioning of sigma(S) between RNAP core and the proteolytic sigma(S)-targeting factor RssB, thereby playing a dual role in fine-tuning sigma(S) proteolysis. In conclusion, Crl
has a key role in reorganising the Escherichia coli transcriptional machinery and global gene expression during entry into stationary phase. The molecular basis of selective promoter activation by the sigmaS
subunit of RNA polymerase. Typas, A., Becker, G. & Hengge, R. Mol Microbiol. 2007 Mar;63(5):1296-306. Different environmental stimuli cause bacteria to exchange the sigma subunit in the RNA polymerase (RNAP)
and, thereby, tune their gene expression according to the newly emerging needs. Sigma factors are usually thought to recognize clearly distinguishable promoter DNA determinants, and thereby activate distinct gene sets,
known as their regulons. In this review, we illustrate how the principle sigma factor in stationary phase and in stressful conditions in Escherichia coli, sigmaS (RpoS), can specifically target its
large regulon in vivo, although it is known to recognize the same core promoter elements in vitro as the housekeeping sigma factor, sigma70 (RpoD). Variable combinations of cis-acting promoter features
and trans-acting protein factors determine whether a promoter is recognized by RNAP containing sigmaS or sigma70, or by both holoenzymes. How these promoter features impose sigmaS selectivity is further discussed.
Moreover, additional pathways allow sigmaS to compete more efficiently than sigma70 for limiting amounts of core RNAP (E) and thereby enhance EsigmaS formation and effectiveness. Finally, these topics are discussed
in the context of sigma factor evolution and the benefits a cell gains from retaining competing and closely related sigma factors with overlapping sets of target genes. The -35 sequence
location and the Fis-sigma factor interface determine sigmas selectivity of the proP (P2) promoter in Escherichia coli. Typas, A., Stella, S., Johnson, R.C. & Hengge, R. Mol Microbiol. 2007 Feb;63(3):780-96.
The P2 promoter of proP, encoding a transporter for proline and glycine betaine in Escherichia coli, is a unique paradigm, where master regulators of different growth stages, Fis and sigma(S)
(RpoS), collaborate to achieve promoter activation. It is also the only case described where Fis functions as class II transcriptional activator (centred at -41). Here we show that the degenerate
-35 sequence, and the location of the Fis binding site, which forces a suboptimal 16 bp spacing between the -35 and -10 elements, allow only sigma(S) but not sigma(70) to
function at proP (P2). Moreover, the interface between Fis and sigma(S) seems better suited to sigma(S), due to a single residue difference between sigma(S) and sigma(70). Nevertheless, Fis can activate
RNA polymerase containing sigma(70) at a proP (P2) promoter variant, in which a typical sigma(70)-35 recognition sequence has been introduced at a 17 bp distance from the -10 hexamer. In
summary, we elucidate the rules that govern sigma factor selectivity in the presence of a class II activator, provide new insight into transcriptional activation by Fis from this position, and
clarify, why the proP (P2) promoter is precisely activated during a short time window of the growth cycle, when Fis and sigma(S) are both present. The sigmaS subunit of RNA
polymerase as a signal integrator and network master regulator in the general stress response in Escherichia coli. Klauck, E., Typas, A. & Hengge, R. Sci Prog. 2007;90(Pt 2-3):103-27. The sigmaS
(RpoS) subunit of RNA polymerase in Escherichia coli is a key master regulator which allows this bacterial model organism and important pathogen to adapt to and survive environmentally rough times.
While hardly present in rapidly growing cells, sigmaS strongly accumulates in response to many different stress conditions, partly replaces the vegetative sigma subunit in RNA polymerase and thereby reprograms this
enzyme to transcribe sigmaS-dependent genes (up to 10% of the E. coli genes). In this review, we summarize the extremely complex regulation of sigmaS itself and multiple signal input at
the level of this master regulator, we describe the way in which sigmaS specifically recognizes "stress" promoters despite their similarity to vegetative promoters, and, while being far from comprehensive, we
give a short overview of the far-reaching physiological impact of sigmaS. With sigmaS being a central and multiple signal integrator and master regulator of hundreds of genes organized in regulatory
cascades and sub-networks or regulatory modules, this system also represents a key model system for analyzing complex cellular information processing and a starting point for understanding the complete regulatory network
of an entire cell. Role of the spacer between the -35 and -10 regions in sigmas promoter selectivity in Escherichia coli. Typas, A. & Hengge, R. Mol Microbiol. 2006 Feb;59(3):1037-51.
In vitro, the sigma(s) subunit of RNA polymerase (RNAP), RpoS, recognizes nearly identical -35 and -10 promoter consensus sequences as the vegetative sigma70. In vivo, promoter selectivity of RNAP holoenzyme
containing either sigma(s) (Esigma(s)) or sigma70 (Esigma70) seems to be achieved by the differential ability of the two holoenzymes to tolerate deviations from the promoter consensus sequence. In this study,
we suggest that many natural sigma(s)-dependent promoters possess a -35 element, a feature that has been considered as not conserved among sigma(s)-dependent promoters. These -35 hexamers are mostly non-optimally spaced
from the -10 region, but nevertheless functional. A +/- 2 bp deviation from the optimal spacer length of 17 bp or the complete absence of a -35 consensus sequence decreases
overall promoter activity, but at the same time favours Esigma(s) in its competition with Esigma70 for promoter recognition. On the other hand, the reduction of promoter activity due to shifting
of the -35 element can be counterbalanced by an activity-stimulating feature such as A/T-richness of the spacer region without compromising Esigma(s) selectivity. Based on mutational analysis of sigma(s), we suggest
a role of regions 2.5 and 4 of sigma(s) in sensing sub-optimally located -35 elements. Differential ability of sigma(s) and sigma70 of Escherichia coli to utilize promoters containing half or
full UP-element sites. Typas, A. & Hengge, R. Mol Microbiol. 2005 Jan;55(1):250-60. The sigma(s) subunit of RNA polymerase (RNAP) is the master regulator of the general stress response in Escherichia
coli. Nevertheless, the selectivity of promoter recognition by the housekeeping sigma70-containing and sigma5-containing RNAP holoenzymes (Esigma70 and Esigma(s) respectively) is not yet fully clarified, as they both recognize nearly identical
-35 and -10 promoter consensus sequences. In this study, we show that in a subset of promoters, Esigma(s) favours the presence of a distal UP-element half-site, and at the same
time is unable to take advantage of a proximal half-site or a full UP-element. This is reflected by the frequent occurrence of distal UP-element half-sites in natural sigma(s)-dependent promoters and
the absence of proximal half-sites. Esigma70, however, exhibits the opposite preference. The presence of the -35 element is a prerequisite for this differential behaviour. In the absence of the -35
element, half or full UP-element sites play no role in sigma selectivity, but the distal subsite leads to an equivalent, if not greater, transcriptional stimulation than the proximal one for
both sigma factors. Finally, experiments using single amino acid substitutions of sigma(s) indicate that the foundation for this preference lies in an inability of sigma(s) to interact with the a
Definition of Trichinella spiralis Trichinella spiralis: The worm that causes trichinosis. Trichinella spiralis larvae can infest pigs and wild game, hibernating in muscle tissue within a protective cyst. Trichinosis can
be correspondingly defined as a disease caused by eating raw or undercooked pork or wild game infested with the larvae of the worm Trichinella spiralis. When a human or an
animal eats meat that contains infective Trichinella cysts, the acid in the stomach dissolves the hard covering of the cyst and releases the worms. The worms pass into the small
intestine and, in 1-2 days, become mature. After mating, adult females lay eggs. Eggs develop into immature worms, travel through the arteries, and are transported to muscles. Within the muscles,
the worms curl into a ball and encyst (become enclosed in a capsule). Infection occurs when these encysted worms are consumed in meat.Source: MedTerms™ Medical Dictionary Last Editorial Review: 4/27/2011
5:27:15 PM Medical Dictionary Definitions A - Z Search Medical Dictionary Get the latest treatment options. Digestive Disorders Resources Health Solutions From Our Sponsors Most Popular Topics Pill Identifier on
The Housing Commission of Victoria (HCV) was established by the Victorian Government in 1938 after a public campaign for housing reform led by Methodist layman Oswald Barnett and supported by the Herald newspaper. The founding commissioners (Barnett, Oswald Burt and
social worker Frances Penington) had all contributed to the Report of the Housing Investigation and Slum Abolition Board which documented the impact of the 1930s depression on the social and physical fabric of inner-city Melbourne. The Commission's initial brief was