Cooling rates of chondrules from diffusion profiles in relict olivine grains

Chondrule cooling rates are one of the important constraints on chondrule formation and can be used to distinguish between different chondrule formation mechanisms. Here we have modelled diffusion profiles observed across the boundary between forsteritic-olivine relict grains and more fayalitic overgrowth. We show that the cooling of chondrules is complex and good model fits are produced with non-linear cooling rates, offering additional scope for constraining the origin of chondrules

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Using Technology to Connect Home Culture to Classroom Community

Embracing the cultural diversity of the classroom community instills tolerance and helps children and their families feel comfortable in the learning environment. This presentation explores several methods used by a preschool classroom to connect home culture to classroom community by incorporating technology as a tool

TIPS FOR STUDENTS WITH USHER SYNDROME: Information Sheet

Lists accommodations and adaptations that can be made in a classroom for students with Usher Syndrome. Includes suggestions for lighting, seating, classroom environment, materials, sign language techniques, orientation and mobility, and self-advocacy

Notchless affects the Wnt pathway during pre-implantation development in mice

In order to determine the genetic pathways required for early mammalian fetal development, a positional cloning study was performed using two embryonic lethal lines of mice, l11Jus1, and l11Jus4. These lines were derived from an ENU mutagenesis screen targeted to a 34Mb region of mouse chromosome 11. The mutations were identified for both lines in Notchless (Nle1), a regulator of the Notch pathway, and a gene expression study was initiated. RNA was isolated from wild type and l11Jus1 homozygous embryos for qRT- PCR analysis using a Notch pathway focused PCR array. Genes present on the array include Notch ligands, receptors, target genes, transcription factors, and genes from other related genetic pathways. Very few Notch target genes were misregulated in the mutants, while there was a non-significant down regulation of some of the ligands and receptors. Only Cdkn1a was significantly up-regulated in the mutants. Cdkn1a is a target gene of Notch signaling, but is also involved in apoptosis. Surprisingly, this study revealed a down-regulation of Wnt genes in the mutant embryos during pre-implantation development. Wnt and Notch are known to interact later in development during somitogenesis, but Notch is not required during pre-implantation development. This study shows a component of Notch signaling (i.e. Nle1) interacts with Wnt during peri-implantation in the developing embryo without affecting global Notch signaling. The over-expression of Cdkn1a could result from misregulation of Notch, disruption in another Nle1 dependent pathway during this developmental timepoint or because the embryo is undergoing apoptosis. Therefore, either Notch signaling interacts with Wnt during pre-implantation development, or Nle1 acts through a yet to be identified pathway that alters Wnt signaling