Creating an Exploratory Protocol of Protein Thermodynamics for Chemistry Undergraduates

The objective of this research is to create a protocol that explores the protein unfolding process and its thermodynamic properties using circular dichroism (CD) spectroscopy and differential scanning fluorimetry (DSF) for chemistry undergraduates. The thermodynamic properties of interest for the unfolding process are the standard enthalpy change (ΔH°), the standard entropy changes (ΔS°), the equilibrium constant (K) and melting temperature (Tm). The CD instrument explores these thermodynamic properties by utilizing the thermal denaturation scan (TD scan). Alongside the TD scan, the CD instrument can also explore the makeup of the protein using the wavelength scan (WL scan). The WL scan is able to provide information on the secondary structure of the protein. These results can provide an understanding when exploring the thermodynamic properties of a protein. With the creation of this protocol, it was decided that the students are required design an overall research question with a testable hypothesis. The protocol provided underwent a test run with chemistry students and feedback was obtained. The results of this research found that the protocol for undergraduate chemistry majors provided a well developed understanding of protein thermodynamics and structure

Preceptorship: Creating an Educational Framework for Histotechnology

https://openworks.mdanderson.org/edwk22/1004/thumbnail.jp

Experimental chronic noise is related to elevated fecal corticosteroid metabolites in lekking male greater Sage-Grouse (Centrocercus urophasianus).

There is increasing evidence that individuals in many species avoid areas exposed to chronic anthropogenic noise, but the impact of noise on those who remain in these habitats is unclear. One potential impact is chronic physiological stress, which can affect disease resistance, survival and reproductive success. Previous studies have found evidence of elevated stress-related hormones (glucocorticoids) in wildlife exposed to human activities, but the impacts of noise alone are difficult to separate from confounding factors. Here we used an experimental playback study to isolate the impacts of noise from industrial activity (natural gas drilling and road noise) on glucocorticoid levels in greater sage-grouse (Centrocercus urophasianus), a species of conservation concern. We non-invasively measured immunoreactive corticosterone metabolites from fecal samples (FCMs) of males on both noise-treated and control leks (display grounds) in two breeding seasons. We found strong support for an impact of noise playback on stress levels, with 16.7% higher mean FCM levels in samples from noise leks compared with samples from paired control leks. Taken together with results from a previous study finding declines in male lek attendance in response to noise playbacks, these results suggest that chronic noise pollution can cause greater sage-grouse to avoid otherwise suitable habitat, and can cause elevated stress levels in the birds who remain in noisy areas

Extra argumentality - affectees, landmarks, and voice

This article investigates sentences with additional core arguments of a special type in three languages, viz. German, English, and Mandarin. These additional arguments, called extra arguments in the article, form a crosslinguistically homogeneous class by virtue of their structural and semantic similarities, with so-called "raised possessors" forming just a sub-group among them. Structurally, extra arguments may not be the most deeply embedded arguments in a sentence. Semantically, their referents are felt to stand in a specific relation to the referent of the/a more deeply embedded argument. There are two major thematic relations that are instantiated by extra arguments, viz. affectees and landmarks. These thematic role notions are justified in the context of and partly in contrast to, Dowty's (1991) proto-role approach. An affectee combines proto-agent with proto-patient properties in eventualities that are construed as involving causation. A landmark is a ground with respect to some spatial configuration denoted by the predication at hand, but a figure at the highest level of gestalt partitioning that is relevant in a clause. Thereby, both affectees and landmarks are inherently hybrid categories. The account of extra argumentality is couched in a neo-Davidsonian event semantics in the spirit of Kratzer (1996, 2003), and voice heads are assumed to introduce affectee arguments and landmark arguments right above VP

Mathematical stories: Why do more boys than girls choose to study mathematics at AS-level in England?

Copyright @ 2005 Taylor & FrancisIn this paper I address the question: How is it that people come to choose mathematics and in what ways is this process gendered? I draw on the findings of a qualitative research study involving interviews with 43 young people all studying mathematics in post-compulsory education in England. Working within a post-structuralist framework, I argue that gender is a project and one that is achieved in interaction with others. Through a detailed reading of Toni and Claudia’s stories I explore the tensions for young women who are engaging in mathematics, something that is discursively inscribed as masculine, while (understandably) being invested in producing themselves as female. I conclude by arguing that seeing ‘doing mathematics’ as ‘doing masculinity’ is a productive way of understanding why mathematics is so male dominated and by looking at the implications of this understanding for gender and mathematics reform work.This work is funded by the ESR

Structural features distinguishing infectious ex vivo mammalian prions from non-infectious fibrillar assemblies generated in vitro

Seeded polymerisation of proteins forming amyloid fibres and their spread in tissues has been implicated in the pathogenesis of multiple neurodegenerative diseases: so called "prion-like" mechanisms. While ex vivo mammalian prions, composed of multichain assemblies of misfolded host-encoded prion protein (PrP), act as lethal infectious agents, PrP amyloid fibrils produced in vitro generally do not. The high-resolution structure of authentic infectious prions and the structural basis of prion strain diversity remain unknown. Here we use cryo-electron microscopy and atomic force microscopy to examine the structure of highly infectious PrP rods isolated from mouse brain in comparison to non-infectious recombinant PrP fibrils generated in vitro. Non-infectious recombinant PrP fibrils are 10 nm wide single fibres, with a double helical repeating substructure displaying small variations in adhesive force interactions across their width. In contrast, infectious PrP rods are 20 nm wide and contain two fibres, each with a double helical repeating substructure, separated by a central gap of 8-10 nm in width. This gap contains an irregularly structured material whose adhesive force properties are strikingly different to that of the fibres, suggestive of a distinct composition. The structure of the infectious PrP rods, which cause lethal neurodegeneration, readily differentiates them from all other protein assemblies so far characterised in other neurodegenerative diseases

Prion 2016 poster abstracts

Until now, the 3-dimensional structure of infectious mammalian prions and how this differs from non-infectious amyloid fibrils remained unknown. Mammalian prions are hypothesized to be fibrillar or amyloid forms of prion protein (PrP), but structures observed to date have not been definitively correlated with infectivity. One of the major challenges has been the production of highly homogeneous material of demonstrable high specific infectivity to allow direct correlation of particle structure with infectivity. We have recently developed novel methods to obtain exceptionally pure preparations of prions from prion-infected murine brain and have shown that pathogenic PrP in these high-titer preparations is assembled into rod-like assemblies (Wenborn et al. 2015. Sci. Rep. 10062). Our preparations contain very high titres of infectious prions which faithfully transmit prion strain-specific phenotypes when inoculated into mice making them eminently suitable for detailed structural analysis. We are now undertaking structural characterization of prion assemblies and comparing these to the structure of non-infectious PrP fibrils generated from recombinant Pr

The Potential of MLN3651 in Combination with Selumetinib as a Treatment for Merlin-Deficient Meningioma

Meningioma is the most common primary intracranial tumour, and surgical resection is the main therapeutic option. Merlin is a tumour suppressor protein that is frequently mutated in meningioma. The activity of the E3 ubiquitin ligase complex, CRL4-DCAF1, and the Raf/MEK/ERK scaffold protein Kinase suppressor of Ras 1 (KSR1) are upregulated in Merlin-deficient tumours, which drives tumour growth. Identifying small molecules that inhibit these key pathways may provide an effective treatment option for patients with meningioma. We used meningioma tissue and primary cells derived from meningioma tumours to investigate the expression of DDB1 and Cullin 4-associated factor 1 (DCAF1) and KSR1, and confirmed these proteins were overexpressed. We then used primary cells to assess the therapeutic potential of MLN3651, a neddylation inhibitor which impacts the activity of the CRL family of E3 ubiquitin ligases and the MAPK/ERK kinase (MEK1/2) inhibitor selumetinib. MLN3651 treatment reduced proliferation and activated apoptosis, whilst increasing Raf/MEK/ERK pathway activation. The combination of MLN3651 and the MEK1/2 inhibitor selumetinib prevented the increase in Raf/MEK/ERK activity, and had an additive effect compared with either treatment alone. Therefore, the combined targeting of CRL4-DCAF1 and Raf/MEK/ERK activity represents an attractive novel strategy in the treatment of Merlin-deficient meningioma