A structural comparison of human serum transferrin and human lactoferrin

The transferrins are a family of proteins that bind free iron in the blood and bodily fluids. Serum transferrins function to deliver iron to cells via a receptor-mediated endocytotic process as well as to remove toxic free iron from the blood and to provide an anti-bacterial, low-iron environment. Lactoferrins (found in bodily secretions such as milk) are only known to have an anti-bacterial function, via their ability to tightly bind free iron even at low pH, and have no known transport function. Though these proteins keep the level of free iron low, pathogenic bacteria are able to thrive by obtaining iron from their host via expression of outer membrane proteins that can bind to and remove iron from host proteins, including both serum transferrin and lactoferrin. Furthermore, even though human serum transferrin and lactoferrin are quite similar in sequence and structure, and coordinate iron in the same manner, they differ in their affinities for iron as well as their receptor binding properties: the human transferrin receptor only binds serum transferrin, and two distinct bacterial transport systems are used to capture iron from serum transferrin and lactoferrin. Comparison of the recently solved crystal structure of iron-free human serum transferrin to that of human lactoferrin provides insight into these differences

Functional and regulatory profiling of energy metabolism in fission yeast

Background: The control of energy metabolism is fundamental for cell growth and function and anomalies in it are implicated in complex diseases and ageing. Metabolism in yeast cells can be manipulated by supplying different carbon sources: yeast grown on glucose rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. Growth media and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene-expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in energy metabolism pathways are coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that acetyl-CoA synthase, rather than citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: This study provides a rich framework of the genetic and regulatory basis of energy metabolism in fission yeast and beyond, and it pinpoints weaknesses of commonly used auxotroph mutants for investigating metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast

The blue urban: colouring and constructing Kolkata

Since 2012, Kolkata’s ruling political party has mobilized the colours blue and white in a concerted effort to rejuvenate the city by referencing big urban ambitions, corporate capital and cheerfulness. Opponents, however, assert that as a state imposed colour, blue limits freedom and makes the city un-alluring. This article suggests that Kolkata’s contemporary blue urban gathers momentum as a political force. Colour mediates political power, creating new constituencies via construction and maintenance. Through a close correspondence between the state’s blue (colours of government offices, public infrastructures, urban lattices), the real estate’s blue (promising middle class residential living) and the widespread use of blue as an everyday urban colour (in slums, shutters, tarpaulin and corrugated boundary walls), the city’s contemporary colours undoes its prior forms. Following blue’s differing shades, patterns, and textures, in public spaces, elite residences, construction sites, and slums, I demonstrate how landed families, resettled artisans, and slum dwellers embrace blue as a colour of hope, while grappling with its corrupt and exclusionary forces

A prospective in silico analysis of interdisciplinary and interobserver spatial variability in post-operative target delineation of high-risk oral cavity cancers: Does physician specialty matter?

Background: The aim of this study was to determine the interdisciplinary agreement in identifying the post-operative tumor bed. Methods: Three radiation oncologists (ROs), four surgeons, and three radiologists segmented post-operative tumor and nodal beds for three patients with oral cavity cancer. Specialty cohort composite contours were created by STAPLE algorithm implementation results for interspecialty comparison. Dice similarity coefficient and Hausdorff distance were utilized to compare spatial differentials between specialties. Results: There were significant differences between disciplines in target delineation. There was unacceptable variation in Dice similarity coefficient for each observer and discipline when compared to the STAPLE contours. Within surgery and radiology disciplines, there was good consistency in volumes. ROs and radiologists have similar Dice similarity coefficient scores compared to surgeons. Conclusion: There were significant interdisciplinary differences in perceptions of tissue-at-risk. Better communication and explicit description of at-risk areas between disciplines is required to ensure high-risk areas are adequately targeted