Regulation of haplid phenotypes in Ustilago maydis by ammonium transporters and components of the b mating locus.

Fungi that can switch from budding to a filamentous infectious state have evolved mating type loci. Ustilago maydis, the maize pathogen, must mate with compatible partners possessing different alleles at two mating type loci for successful host infection. The a locus encodes pheromones and receptors, while the b locus encodes subunits of a heterodimeric transcription factor that regulates expression of virulence genes. Mating is triggered by environmental signals, including nutrient deprivation. My goal was to determine the fate of nitrogen starved haploid cells without a compatible mating partner. On solid low ammonium media, wild-type U. maydis filaments. I examined the roles of the b mating locus, and Ump2, the high affinity ammonium transporter, in this phenotype. Expression of ump2 increases under low ammonium, while deletion of b or ump2 results in loss of filamentation. Deleting b did not affect the induction of ump2, but deletion of ump2 altered expression from the b locus. In my model of filamentation on low ammonium, ump2 senses nitrogen availability and, in a b-dependent manner, upregulates targets canonically involved in mating but, without a partner, functions in filamentation. The b locus contains two genes, bE and bW, but the heterodimer does not form in haploid cells. I found evidence that bE and bW function independently in haploids to regulate gene expression. Partial deletion of b also results in loss of filamentation in media depleted of ammonium. Although ump2 overexpression in a b deletion background rescues the loss of filamentous phenotype, this phenomenon is absent when bE remains. This suggests bW regulates transcription of mating and pathogenicity targets in a similar manner to ump2, while bE does so in the opposite direction. Finally, through biofluorescent labelling I visualized the rearrangement of the actin cytoskeleton in response to low ammonium. I also investigated via qRT-PCR several targets, including actin and its regulators, and cell wall remodeling enzymes. Although these targets showed dynamic expression levels in the mutants, no pattern emerged explaining the varied filamentous phenotypes. As such, changes of the actin cytoskeleton upon exposure to low ammonium are not regulated at the transcription level

Of mice and sigma : conferred antibiotic resistance in the Salmonella enterica serovar Typhimurium murine model.

Salmonella enterica serovar Typhimurium is an enteric pathogen capable of infecting a wide range of hosts. The manner in which this pathogen is able to interact with its host is difficult to define, as is the case with most microbes. Through the use of alternate sigma factors and other regulatory processes, S. Typhimurium is able to invade host cells to establish systemic infections, and survive the assaults of the host immune system. While most strains of S. Typhimurium are typically ampicillin sensitive, within the host, survival inside host cells may provide an escape from many antibiotics. Previous research demonstrated that co-culture with ampicillin resistant strains of Escherichia coli is able to provide protection for sensitive S. Typhimurium. The current study was an attempt to model this relationship within the host. While S. Typhimurium was able to grow within murine hosts in the presence of ampicillin, it is unclear whether this resistance is from coinfection with a resistant strain of E. coli or from the ability of S. Typhimurium to avoid destruction by antibiotics by invading host cells

Interview with Half Century Club Inductees, Class of 1930

Oral history interview with Illinois State Normal University alumni, Class of 1930. The interview was conducted on May 10, 1980, by an unidentified interviewer. They discuss President Felmley, influential faculty, and racial discrimination experienced by students of color.https://ir.library.illinoisstate.edu/aoh/1002/thumbnail.jp

Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats

. In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat. D-galactosamine (D-gal) was used to selectively inhibit liver protein synthesis. D-gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 g/kg ip) was injected 24 h post-heat exposure. Treatment with D-gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with D-gal and subsequently with LPS demonstrated a profound fall in core temperature 10-18 h post-LPS. A significant increase of serum TNF-␣ accompanied this effect of D-gal on fever. Heat-conditioned animals receiving D-gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS. heat shock proteins; liver; heart; kidney; tumor necrosis factor-␣, interleukin-6, temperature regulation; fever; lipopolysaccharide HEAT STRESS PROVOKES metabolic adaptations in the whole organism. One such response is the production of heat shock proteins (HSPs) (26). The accumulation of HSPs within cells helps both cells and the whole organism survive subsequent, otherwise lethal, thermal stress. Interestingly, heat conditioning sufficient to cause cellular HSP accumulation has also been shown to be protective in a subsequent, otherwise lethal, endotoxin challenge (30). Several studies have demonstrated that HSPs regulate cytokine production in peripheral blood monocytes. Intracellular HSP accumulation is associated with a decrease in synthesis of tumor necrosis factor-␣ (TNF-␣) and interleukin (IL)-1␤ (6, 32). Impaired HSP production causes enhanced TNF-induced cytotoxicity in cells Whereas heat conditioning is protective, pretreatment with D-galactosamine (D-gal) increases sensitivity to subsequent LPS (2, 10). D-gal inhibits protein synthesis primarily in the live

Stakeholder consensus for decision making in eye-gaze control technology for children, adolescents and adults with cerebral palsy service provision: findings from a Delphi study.

BACKGROUND: Limited research exists to guide clinical decisions about trialling, selecting, implementing and evaluating eye-gaze control technology. This paper reports on the outcomes of a Delphi study that was conducted to build international stakeholder consensus to inform decision making about trialling and implementing eye-gaze control technology with people with cerebral palsy. METHODS: A three-round online Delphi survey was conducted. In Round 1, 126 stakeholders responded to questions identified through an international stakeholder Advisory Panel and systematic reviews. In Round 2, 63 respondents rated the importance of 200 statements generated by in Round 1. In Round 3, 41 respondents rated the importance of the 105 highest ranked statements retained from Round 2. RESULTS: Stakeholders achieved consensus on 94 of the original 200 statements. These statements related to person factors, support networks, the environment, and technical aspects to consider during assessment, trial, implementation and follow-up. Findings reinforced the importance of an individualised approach and that information gathered from the user, their support network and professionals are central when measuring outcomes. Information required to support an application for funding was obtained. CONCLUSION: This Delphi study has identified issues which are unique to eye-gaze control technology and will enhance its implementation with people with cerebral palsy

Integrating team science into interdisciplinary graduate education: an exploration of the SESYNC Graduate Pursuit

Complex socio-environmental challenges require interdisciplinary, team-based research capacity. Graduate students are fundamental to building such capacity, yet formal opportunities for graduate students to develop these capacities and skills are uncommon. This paper presents an assessment of the Graduate Pursuit (GP) program, a formal interdisciplinary team science graduate research and training program administered by the National Socio-Environmental Synthesis Center (SESYNC). Quantitative and qualitative assessment of the program’s first cohort revealed that participants became significantly more comfortable with interdisciplinary research and team science approaches, increased their capacity to work across disciplines, and were enabled to produce tangible research outcomes. Qualitative analysis of four themes—(1) discipline, specialization, and shared purpose, (2) interpersonal skills and personality, (3) communication and teamwork, and (4) perceived costs and benefits—encompass participants’ positive and negative experiences and support findings from past assessments. The findings also identify challenges and benefits related to individual personality traits and team personality orientation, the importance of perceiving a sense of autonomy and independence, and the benefit of graduate training programs independent of the university and graduate program environment

Minimising impairment: Protocol for a multicentre randomised controlled trial of upper limb orthoses for children with cerebral palsy.

BACKGROUND: Upper limb orthoses are frequently prescribed for children with cerebral palsy (CP) who have muscle overactivity predominantly due to spasticity, with little evidence of long-term effectiveness. Clinical consensus is that orthoses help to preserve range of movement: nevertheless, they can be complex to construct, expensive, uncomfortable and require commitment from parents and children to wear. This protocol paper describes a randomised controlled trial to evaluate whether long-term use of rigid wrist/hand orthoses (WHO) in children with CP, combined with usual multidisciplinary care, can prevent or reduce musculoskeletal impairments, including muscle stiffness/tone and loss of movement range, compared to usual multidisciplinary care alone. METHODS/DESIGN: This pragmatic, multicentre, assessor-blinded randomised controlled trial with economic analysis will recruit 194 children with CP, aged 5-15 years, who present with flexor muscle stiffness of the wrist and/or fingers/thumb (Modified Ashworth Scale score =1). Children, recruited from treatment centres in Victoria, New South Wales and Western Australia, will be randomised to groups (1:1 allocation) using concealed procedures. All children will receive care typically provided by their treating organisation. The treatment group will receive a custom-made serially adjustable rigid WHO, prescribed for 6 h nightly (or daily) to wear for 3 years. An application developed for mobile devices will monitor WHO wearing time and adverse events. The control group will not receive a WHO, and will cease wearing one if previously prescribed. Outcomes will be measured 6 monthly over a period of 3 years. The primary outcome is passive range of wrist extension, measured with fingers extended using a goniometer at 3 years. Secondary outcomes include muscle stiffness, spasticity, pain, grip strength and hand deformity. Activity, participation, quality of life, cost and cost-effectiveness will also be assessed. DISCUSSION: This study will provide evidence to inform clinicians, services, funding agencies and parents/carers of children with CP whether the provision of a rigid WHO to reduce upper limb impairment, in combination with usual multidisciplinary care, is worth the effort and costs. TRIAL REGISTRATION: ANZ Clinical Trials Registry: U1111-1164-0572

Cognition and bimanual performance in children with unilateral cerebral palsy: Protocol for a multicentre, cross-sectional study

© 2018 The Author(s). Background: Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. Methods/Design: This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. Discussion: This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations