Increased accuracy of ligand sensing by receptor internalization

Many types of cells can sense external ligand concentrations with cell-surface receptors at extremely high accuracy. Interestingly, ligand-bound receptors are often internalized, a process also known as receptor-mediated endocytosis. While internalization is involved in a vast number of important functions for the life of a cell, it was recently also suggested to increase the accuracy of sensing ligand as the overcounting of the same ligand molecules is reduced. Here we show, by extending simple ligand-receptor models to out-of-equilibrium thermodynamics, that internalization increases the accuracy with which cells can measure ligand concentrations in the external environment. Comparison with experimental rates of real receptors demonstrates that our model has indeed biological significance.Comment: 9 pages, 4 figures, accepted for publication in Physical Review

The initial education of high school teachers : a critical review of major issues and trends

This paper draws on major research findings in international literature in order to provide a critical review of a number of key issues and trends in the initial education of high school teachers. Firstly, this paper contextualizes the prevalent discourse surrounding the field of initial teacher education (ITE) and explores the effect that this discourse has on the conceptualization of teachers’ work. Secondly, this paper focuses on the debates regarding the most propitious site for the teacher education enterprise, the programme structure for ITE, the field placement or practicum, the relationship between subject study and pedagogy, and the overall effectiveness of teacher education. The paper concludes by considering the new challenges that the field of initial teacher education must confront and the implications of such challenges for the ITE curriculum.peer-reviewe

Regulation of Alr1 Mg Transporter Activity by Intracellular Magnesium

Mg homeostasis is critical to eukaryotic cells, but the contribution of Mg transporter activity to homeostasis is not fully understood. In yeast, Mg uptake is primarily mediated by the Alr1 transporter, which also allows low affinity uptake of other divalent cations such as Ni2+, Mn2+, Zn2+ and Co2+. Using Ni2+ uptake to assay Alr1 activity, we observed approximately nine-fold more activity under Mg-deficient conditions. The mnr2 mutation, which is thought to block release of vacuolar Mg stores, was associated with increased Alr1 activity, suggesting Alr1 was regulated by intracellular Mg supply. Consistent with a previous report of the regulation of Alr1 expression by Mg supply, Mg deficiency and the mnr2 mutation both increased the accumulation of a carboxy-terminal epitope-tagged version of the Alr1 protein (Alr1-HA). However, Mg supply had little effect on ALR1 promoter activity or mRNA levels. In addition, while Mg deficiency caused a seven-fold increase in Alr1-HA accumulation, the N-terminally tagged and untagged Alr1 proteins increased less than two-fold. These observations argue that the Mg-dependent accumulation of the C-terminal epitope-tagged protein was primarily an artifact of its modification. Plasma membrane localization of YFP-tagged Alr1 was also unaffected by Mg supply, indicating that a change in Alr1 location did not explain the increased activity we observed. We conclude that variation in Alr1 protein accumulation or location does not make a substantial contribution to its regulation by Mg supply, suggesting Alr1 activity is directly regulated via as yet unknown mechanisms

Interaction of the Deubiquitinating Enzyme Ubp2 and the E3 Ligase Rsp5 Is Required for Transporter/Receptor Sorting in the Multivesicular Body Pathway

Protein ubiquitination is essential for many events linked to intracellular protein trafficking. We sought to elucidate the possible involvement of the S. cerevisiae deubiquitinating enzyme Ubp2 in transporter and receptor trafficking after we (this study) and others established that affinity purified Ubp2 interacts stably with the E3 ubiquitin ligase Rsp5 and the (ubiquitin associated) UBA domain containing protein Rup1. UBP2 interacts genetically with RSP5, while Rup1 facilitates the tethering of Ubp2 to Rsp5 via a PPPSY motif. Using the uracil permease Fur4 as a model reporter system, we establish a role for Ubp2 in membrane protein turnover. Similar to hypomorphic rsp5 alleles, cells deleted for UBP2 exhibited a temporal stabilization of Fur4 at the plasma membrane, indicative of perturbed protein trafficking. This defect was ubiquitin dependent, as a Fur4 N-terminal ubiquitin fusion construct bypassed the block and restored sorting in the mutant. Moreover, the defect was absent in conditions where recycling was absent, implicating Ubp2 in sorting at the multivesicular body. Taken together, our data suggest a previously overlooked role for Ubp2 as a positive regulator of Rsp5-mediated membrane protein trafficking subsequent to endocytosis

Innovation in curriculum: An overview

Innovation in curriculum is gaining its thrust from a new set of value priorities—humanism, concern for racial and socioeconomic minorities, support of pluralism and diversity, increased interest in affective development, education for the very young, and legitimization of the search for value. These priorities are coupled with new understandings of how learning takes place, which cast the learner in an active, responsible, self-actualizing role and, at the same time, support the development of precise, highly organized sets of learning materials designed to achieve clearly defined objectives as efficiently as possible. Implications of these factors are examined in relation to curriculum design, instructional materials, professional roles, and the need for in-service education. L'innovation des programmes d'étude est activée par une nouvelle échelle de priorités des valeurs: esprit d'humanisme, intérêt manifesté à l'égard des minorités raciales et socio-économiques, appui accordé au pluralisme et à la diversité, intérêt accru envers le développement affectif, éducation des très jeunes, et légitimisation de la recherche des valeurs. Ces priorités vont de pair avec de nouvelles connaissances sur le processus d'acquisition du savoir, connaissances qui lancent l'élève dans un rôle actif et responsable dans son épanouissement personnel et qui, en même temps, contribuent à la mise au point d'une série de textes éducatifs précis et hautement organisés conçus en vue de la poursuite, d'une manière aussi efficace que possible, de certains objectifs clairement définis. L'auteur étudie les répercussions provoquées par ces facteurs sur la conception des programmes, les textes d'étude, les rôles professionnels et la nécessité d'une éducation en cours d'exercice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42937/1/10780_2005_Article_BF02137640.pd