Palladin Compensates for the Arp2/3 Complex and Supports Actin Structures during Listeria Infections

Palladin is an important component of motile actin-rich structures and nucleates branched actin filament arrays in vitro. Here we examine the role of palladin during Listeria monocytogenes infections in order to tease out novel functions of palladin. We show that palladin is co-opted by L. monocytogenes during its cellular entry and intracellular motility. Depletion of palladin resulted in shorter and misshapen comet tails, and when actin- or VASP-binding mutants of palladin were overexpressed in cells, comet tails disintegrated or became thinner. Comet tail thinning resulted in parallel actin bundles within the structures. To determine whether palladin could compensate for the Arp2/3 complex, we overexpressed palladin in cells treated with the Arp2/3 inhibitor CK-666. In treated cells, bacterial motility could be initiated and maintained when levels of palladin were increased. To confirm these findings, we utilized a cell line depleted of multiple Arp2/3 complex subunits. Within these cells, L. monocytogenes failed to generate comet tails. When palladin was overexpressed in this Arp2/3 functionally null cell line, the ability of L. monocytogenes to generate comet tails was restored. Using purified protein components, we demonstrate that L. monocytogenes actin clouds and comet tails can be generated (in a cell-free system) by palladin in the absence of the Arp2/3 complex. Collectively, our results demonstrate that palladin can functionally replace the Arp2/3 complex during bacterial actin-based motility

The double pendulum

Policy discourses posit an accountability deficit as an underlying cause of a “learning crisis” in many low-income countries. Many studies understand this perceived deficit from a principal-agent perspective, arguing that incentives facing teachers and schools often do not align to the interests of parents and students. Such perspectives underlie many randomized controlled trials, which associate interventions with outcomes, but which also produce varying or inconsistent results across contexts. This paper seeks to study the accountability of schools and teachers more directly, looking at how it varies across public and private schools and how it relates to students’ literacy and numeracy abilities. We report results from a mixed methods study conducted in Mumbai and Kathmandu. Our results show that there are some relationships between accountability and learning outcomes, but these appear to be specific to the context. Quantitative data also show that differences between public and private models of schooling are negligible when students’ social backgrounds and school composition are considered. Qualitative data show that accountability processes create a significant burden on staff time and embed complex power dynamics that are not always productive. Taken together, these results problematize policies that seek to improve learning through “demand-side” approaches such as privatization. They show that the dynamics of accountability are a complex system, like the motion of a “double pendulum,” and therefore simple conceptual approaches such as the principal-agent model are of limited academic and practical utility

Academic training in oral and maxillofacial surgery - when and how to enter the pathway

Entering into surgical academia can seem a daunting prospect for an oral and maxillofacial surgery (OMFS) trainee. However, the streamlining of academic training by the NIHR to create the integrated academic training (IAT) pathway has simplified academic training and more clearly defined academic positions and entry points for trainees. In this article we review the current NIHR IAT pathway and the various grades and entry points available to OMF surgeons, both pre- and post-doctoral. We highlight the unique challenges facing OMF trainees and provide advice and insight from both junior and senior OMFS academics. Finally, we focus on the planning and application for a doctoral research fellowship - discussing funding streams available to OMF surgeons

Women candidates and party nomination trends in India: evidence from the 2009 general election

More women MPs than ever before were elected to the lower house of the national parliament of India in the 2009 General Election. Yet, the increase in women’s presence in the Lok Sabha cannot necessarily be attributed to the increased willingness of political parties to field more women candidates, despite rhetorical party political support for increasing women’s participation in political institutions. This article analyses party political nomination of women as candidates in the 2009 election, and finds significant variations in levels of nomination across parties and across India’s states. The article also examines in detail the nomination of female candidates by the two largest political parties, the Indian National Congress party and the Bharatiya Janata Party, both of which support proposals for introducing reserved seats for women in national and state legislatures. The findings reject the proposition that parties only nominate women in unwinnable seats, but finds support for the proposition that parties are risk averse when it comes to nominating women, and that this can restrict the number of women nominated for election. The article concludes with some further questions for future research on gender and political recruitment in India

1H NMR-Based Metabolic Signatures in the Liver and Brain in a Rat Model of Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a debilitating neuropsychiatric complication associated with acute and chronic liver failure. It is characterized by diverse symptoms with variable severity that includes cognitive and motor deficits. The aim of the study is to assess metabolic alterations in the brain and liver using nuclear magnetic resonance (NMR) spectroscopy and subsequent multivariate analyses to characterize metabolic signatures associated with HE. HE was developed by bile duct ligation (BDL) that resulted in hepatic dysfunctions and cirrhosis as shown by liver function tests. Metabolic profiles from control and BDL rats indicated increased levels of lactate, branched-chain amino acids (BCAAs), glutamate, and choline in the liver, whereas levels of glucose, phenylalanine, and pyridoxine were decreased. In brain, the levels of lactate, acetate, succinate, citrate, and malate were increased, while glucose, creatine, isoleucine, leucine, and proline levels were decreased. Furthermore, neurotransmitters such as glutamate and GABA were increased, whereas choline and myo-inositol were decreased. The alterations in neurotransmitter levels resulted in cognitive and motor defects in BDL rats. A significant correlation was found among alterations in NAA/choline, choline/creatine, and NAA/creatine with behavioral deficits. Thus, the data suggests impairment in metabolic pathways such as the tricarboxylic acid (TCA) cycle, glycolysis, and ketogenesis in the liver and brain of animals with HE. The study highlights that metabolic signatures could be potential markers to monitor HE progression and to assess therapeutic interventions