A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2

<p>Abstract</p> <p>Background</p> <p>Metabolic reconstructions (MRs) are common denominators in systems biology and represent biochemical, genetic, and genomic (BiGG) knowledge-bases for target organisms by capturing currently available information in a consistent, structured manner. <it>Salmonella enterica </it>subspecies I serovar Typhimurium is a human pathogen, causes various diseases and its increasing antibiotic resistance poses a public health problem.</p> <p>Results</p> <p>Here, we describe a community-driven effort, in which more than 20 experts in <it>S</it>. Typhimurium biology and systems biology collaborated to reconcile and expand the <it>S</it>. Typhimurium BiGG knowledge-base. The consensus MR was obtained starting from two independently developed MRs for <it>S</it>. Typhimurium. Key results of this reconstruction jamboree include i) development and implementation of a community-based workflow for MR annotation and reconciliation; ii) incorporation of thermodynamic information; and iii) use of the consensus MR to identify potential multi-target drug therapy approaches.</p> <p>Conclusion</p> <p>Taken together, with the growing number of parallel MRs a structured, community-driven approach will be necessary to maximize quality while increasing adoption of MRs in experimental design and interpretation.</p

Complex cell shape: Molecular mechanisms of tracheal terminal cell development in Drosophila melanogaster

Drosophila larval tracheal terminal cells are highly branched cells with subcellular tubes for gas transport running through their branches. As they grow rapidly over a few days they produce a large quantity of membrane for delivery to both the outer plasma membrane and the plasma membrane making up the subcellular tube. We have found that two proteins involved in membrane vesicle trafficking, Rab8 and tango1, first identified in a small-scale RNAi screen and a MARCM screen, play important roles in terminal cell development. The depletion of Rab8, a small GTPase involved in trans-Golgi network-to-plasma membrane trafficking, results in reduced number of branching points and abnormal tube morphology as a result of reduced membrane delivery to the basolateral membrane. The depletion of Tango1, a transmembrane protein required for the loading of collagen into vesicles at the endoplasmic reticulum exit sites, in terminal cells results in reduced number of branching points, as well as defective luminal air-filling in a collagen-independent manner. Additionally, we show that Drosophila Tango1 is required for the delivery of multiple transmembrane and secreted proteins from the ER, suggesting a more general role for Drosophila Tango1 in trafficking of molecules from ER to Golgi than its mammalian counterpart. For the discovery of genes involved in terminal cell development a quantitative evaluation of defects is important. Therefore, we designed an unbiased quantitative scheme analyzing cellular morphology of terminal cells using imaging and automated quantification. An unbiased quantitative approach allows for comparison of wild type and genetically modified terminal cells. As many genes identified in terminal cell development are conserved in mammals, these studies can shed a light on analogous pathways

Gersveppastofnar til framleiðslu lyfjaefna. Áhrif breytinga á tRNA genum á tjáningu utanaðkomandi próteina

Gersveppir (Saccharomyces cerevisae) hafa lengi verið notaðir til baksturs og bruggunar. Með aukinni þekkingu á gerð og starfsháttum erfðamengis gersveppa opnast möguleikar til framleiðslu á margvíslegum efnum með ódýrari, öruggari og hentugri hætti en verið hefur. Nokkur verðmæt efni eru nú framleidd á þennan hátt, m.a. sterahormónar og malaríulyf, en í rannsóknum okkar og fleiri hafa komið í ljós verulegar hindranir við framleiðslu ýmissa áhugaverðra efna, m.a. fjölketíðefna en meðal þeirra eru svonefnd statin lyf. Nýlega birtar rannsóknir benda til þess að algjör skortur á tjáningu sumra utanaðkomandi gena í gersveppum og öðrum lífverum kunni að stafa af mismun í notkun táknaþrennda. Ákveðnar táknaþrenndir eru lítið notaðar í gersveppum og lítið magn er af þeim tRNA sameindum sem þýða þessar þrenndir. Í þessu verkefni verður kannað hversu mikil áhrif sjaldgæfir táknar hafa á þýðingu, hvaða táknar koma þar helst við sögu og hversu margir þeir þurfa að vera. Jafnframt verður kannað hvort aflétta megi þýðingarhindrun með því að auka fjölda samsvarandi tRNA gena. Þær upplýsingar sem aflað verður munu hafa víðtækt notagildi í gerjunar- og lyfjaiðnaði, sérstaklega við tjáningu utanaðkomandi gena, sem og í almennum gersvepparannsóknum

Vöðvalengd aftanlærisvöðva hjá hlaupurum. Kvenhlauparar bornir saman við almenning og kvenhlaupara sem stunda jóga

Tilgangur: Kanna hvort munur væri á lengd aftanlærisvöðva hjá þremur hópum kvenna, 30-45 ára. Hópur 1 voru konur sem hlaupa a.m.k. 25 km á viku og stunda jóga ≥1 sinni í viku; hópur 2 voru konur sem hlaupa ≥25 km á viku; hópur 3 voru konur sem stunda almenna líkamsrækt ≥3 sinnum í viku (almenningur). Deilt er um hvort liðleiki sé ákjósanlegur fyrir kvenhlaupara og vildum við því skoða það nánar. Aðferð: Þátttakendur voru valdir með hentugleikaúrtaki. Niðurstöður fengust frá mælingum á 36 konum. Þátttakendur svöruðu spurningalista um hreyfingu og meiðsli og svo var aftanlærisvöðvalengd mæld með Óvirkri hnéréttu (Passive knee extension). Þátttakendur þurftu að hafa verið án aftanlærismeiðsla í sex mánuði áður en mælingar hófust. Niðurstöður: Þegar hóparnir voru bornir saman fékkst marktækur munur á milli hóps 1 og 2 og hóps 2 og 3, en ekki á milli hóps 1 og 3. Því mátti sjá að aftanlærisvöðvalengd var marktækt meiri hjá almenningi (3) en hjá hlaupurum (2) (p=0,042). Hlauparar sem stunda jóga voru með marktækt lengri aftanlærisvöðva en hinir hlaupararnir (p=0,0006). Ekki var munur á vöðvalengd hjá hlaupurum sem stunda jóga og almenningi (p=0,092). Samantekt: Niðurstöður sýndu að kvenhlauparar voru með styttri aftanlærisvöðva en almenningur. Einnig voru kvenhlauparar með styttri aftanlærisvöðva en kvenhlauparar sem stunduðu jóga. Rannsóknir í dag hafa ekki getað sýnt fram á aukinn árangur eða lægri meiðslatíðni með bættum liðleika. Sé bættur árangur markmiðið í hlaupi eru teygjur mögulega ekki besti kosturinn. Þó teljum við að jóga sé ákjósanlegt fyrir hlaupara til að auka vellíðan og slökun.Purpose: To see if a difference could be found in the length of the hamstring muscles between three groups of women aged 30-45. Group 1 included women who run ≥25 km a week; group 2 included women who run ≥25 km a week and practice yoga at least once a week; and group 3 included women who do physical exercise ≥3 times a week. There have been debates about whether flexibility is in fact preferable for women who practise running and so we wanted to reflect upon that subject. Methods: Participants were selected at random. Results were obtained from 36 women. Participants answered questionnaires about physical activity and injuries and the hamstrings muscle length was measured with passive knee extension (PKE). Participants had to have been without hamstrings injury for six months before measurements began. Results: When the groups were compared a significant difference was found between group 1 and 2 and between 2 and 3, but not between 1 and 3. Hamstrings muscle length was significantly greater in the general population(3) than in the runners(2) (p=0.042). Runners who practiced yoga had significantly greater hamstrings muscle length than the runners(2) (p=0.0006). There was no difference in muscle length between runners who practiced yoga and the general population (p=0.092). Conclusion: The results showed that female runners had shorter hamstring muscles than the general population. Female runners also had shorter hamstring muscle than female runners who practiced yoga. Studies today have not been able to demonstrate higher performance or lower injury rate with improved flexibility. If improved performance in running is the goal, stretching may not be the best option. However, we believe that yoga is desirable for the runners for ease and relaxation

MITF reprograms the extracellular matrix and focal adhesion in melanoma

The microphthalmia-associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here, we show that MITF directly represses the expression of genes associated with the extracellular matrix (ECM) and focal adhesion pathways in human melanoma cells as well as of regulators of epithelial-to-mesenchymal transition (EMT) such as CDH2, thus affecting cell morphology and cell-matrix interactions. Importantly, we show that these effects of MITF are reversible, as expected from the rheostat model. The number of focal adhesion points increased upon MITF knockdown, a feature observed in drug-resistant melanomas. Cells lacking MITF are similar to the cells of minimal residual disease observed in both human and zebrafish melanomas. Our results suggest that MITF plays a critical role as a repressor of gene expression and is actively involved in shaping the microenvironment of melanoma cells in a cell-autonomous manner