Experimental rodent models of brainstem tumors

Despite recent advances in surgical technology, resection is not an option for many brainstem tumors. Experimental models have played essential roles in examining new approaches to therapy. The objective of the present study was to generate models by determining coordinates for safe inoculation into the brainstem of mice and rats, and to establish whether the implantation of heterotopic cells would create reproducible survival curves. Morbidity and survival studies were used to map stereotactic coordinates allowing successful inoculation of tumor cells. Survival studies were used to investigate the time course of tumor growth. Tumor location was examined by light microscopy and magnetic resonance imaging. Mice survived injections of 2 microL of saline at interaural, lateral, and depth coordinates of -2.5, 1.0, and 3.5 mm and -1.5, 1.0, and 3.5 mm. Rats survived injections at interaural, lateral, and depth coordinates of -2.0, 2.0, and 7.0 mm and -3.0, 0, and 7.0 mm. Median survival of mice challenged with 5 x 10(5) EMT6 and 10(4) B16 tumor cells was 11 and 10 days, respectively. Median survival for rats challenged with 10(4) 9L and F98 cells was 14 and 13 days, respectively. The present study demonstrates a feasible approach to preparing models of brainstem tumors. Limitations of these models are discussed

An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Spatial Stereoresolution for Depth Corrugations May Be Set in Primary Visual Cortex

Stereo “3D” depth perception requires the visual system to extract binocular disparities between the two eyes' images. Several current models of this process, based on the known physiology of primary visual cortex (V1), do this by computing a piecewise-frontoparallel local cross-correlation between the left and right eye's images. The size of the “window” within which detectors examine the local cross-correlation corresponds to the receptive field size of V1 neurons. This basic model has successfully captured many aspects of human depth perception. In particular, it accounts for the low human stereoresolution for sinusoidal depth corrugations, suggesting that the limit on stereoresolution may be set in primary visual cortex. An important feature of the model, reflecting a key property of V1 neurons, is that the initial disparity encoding is performed by detectors tuned to locally uniform patches of disparity. Such detectors respond better to square-wave depth corrugations, since these are locally flat, than to sinusoidal corrugations which are slanted almost everywhere. Consequently, for any given window size, current models predict better performance for square-wave disparity corrugations than for sine-wave corrugations at high amplitudes. We have recently shown that this prediction is not borne out: humans perform no better with square-wave than with sine-wave corrugations, even at high amplitudes. The failure of this prediction raised the question of whether stereoresolution may actually be set at later stages of cortical processing, perhaps involving neurons tuned to disparity slant or curvature. Here we extend the local cross-correlation model to include existing physiological and psychophysical evidence indicating that larger disparities are detected by neurons with larger receptive fields (a size/disparity correlation). We show that this simple modification succeeds in reconciling the model with human results, confirming that stereoresolution for disparity gratings may indeed be limited by the size of receptive fields in primary visual cortex

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Maltreated children use more grammatical negations

Many studies reveal a strong impact of childhood maltreatment on language development, mainly resulting in shorter utterances, less rich vocabulary, or a delay in grammatical complexity. However, different theories suggest the possibility for resilience – a positive adaptation to an otherwise adverse environment – in children who experienced childhood maltreatment. Here, we investigated different measures for language development in spontaneous speech, examining whether childhood maltreatment leads to a language deficit only or whether it can also result in differences in language use due to a possible adaptation to a toxic environment. We compared spontaneous speech during therapeutic peer-play sessions of 32 maltreated and 32 non-maltreated children from the same preschool and equivalent in gender, age (2 to 5 years), home neighborhood, ethnicity, and family income. Maltreatment status was reported by formal child protection reports, and corroborated by independent social service reports. We investigated general language sophistication (i.e., vocabulary, talkativeness, mean length of utterance), as well as grammatical development (i.e., use of plurals, tense, grammatical negations). We found that maltreated and non-maltreated children showed similar sophistication across all linguistic measures, except for the use of grammatical negations. Maltreated children used twice as many grammatical negations as non-maltreated children. The use of this highly complex grammatical structure shows an advanced linguistic skill, which shows that childhood maltreatment does not necessarily lead to a language deficit. The result might indicate the development of a negativity bias in the structure of spontaneous language due to an adaptation to their experiences

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Culture and Subjectivity in Neoliberal and postfeminist times

My aim in this paper is to think through a number of issues concerning the relationship between culture and subjectivity. It seems to me that exploring the relationship of changing forms of political organisation, social relations and cultural practices to changing modes and experiences of subjecthood and subjectivity are among the most important and urgent tasks for critical intellectual work. These questions go to the heart of understanding power, ideology and agency and they require research that is interdisciplinary, psychosocial and intersectional. My particular focus in this short article is on the interrelations between changing representational practices in visual culture and changing subjectivity/ies. I argue that neoliberalism and postfeminism are central to understanding contemporary media culture, and I put the case for research which does not retreat from exploring how these broader social/political/economic/cultural discourses and formations may relate to subjectivity

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

A systematic review of rodent pest research in Afro-Malagasy small-holder farming systems: Are we asking the right questions?

Rodent pests are especially problematic in terms of agriculture and public health since they can inflict considerable economic damage associated with their abundance, diversity, generalist feeding habits and high reproductive rates. To quantify rodent pest impacts and identify trends in rodent pest research impacting on small-holder agriculture in the Afro-Malagasy region we did a systematic review of research outputs from 1910 to 2015, by developing an a priori defined set of criteria to allow for replication of the review process. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We reviewed 162 publications, and while rodent pest research was spatially distributed across Africa (32 countries, including Madagascar), there was a disparity in number of studies per country with research biased towards four countries (Tanzania [25%], Nigeria [9%], Ethiopia [9%], Kenya [8%]) accounting for 51% of all rodent pest research in the Afro-Malagasy region. There was a disparity in the research themes addressed by Tanzanian publications compared to publications from the rest of the Afro-Malagasy region where research in Tanzania had a much more applied focus (50%) compared to a more basic research approach (92%) in the rest of the Afro-Malagasy region. We found that pest rodents have a significant negative effect on the Afro-Malagasy small-holder farming communities. Crop losses varied between cropping stages, storage and crops and the highest losses occurred during early cropping stages (46% median loss during seedling stage) and the mature stage (15% median loss). There was a scarcity of studies investigating the effectiveness of various management actions on rodent pest damage and population abundance. Our analysis highlights that there are inadequate empirical studies focused on developing sustainable control methods for rodent pests and rodent pests in the Africa-Malagasy context is generally ignored as a research topic

Study protocol: a mixed methods feasibility study for a loaded self-managed exercise programme for patellofemoral pain

Background: Patellofemoral pain (PFP) is one of the most common forms of knee pain in adults under the age of 40, with a prevalence of 23% in the general population. The long-term prognosis is poor, with only one third of people pain-free 1 year after diagnosis. The biomedical model of pain in relation to persistent PFP has recently been called into question. It has been suggested that interventions for chronic musculoskeletal conditions should consider alternative mechanisms of action, beyond muscles and joints. Modern treatment therapies should consider desensitising strategies, with exercises that target movements and activities patients find fearful and painful. High-quality research on exercise prescription in relation to pain mechanisms, not directed at specific tissue pathology, and dose response clearly warrants further investigation. Our primary aim is to establish the feasibility and acceptability of conducting a definitive RCT which will evaluate the clinical and cost-effectiveness of a loaded self-managed exercise programme for people with patellofemoral pain. Method: This is a single-centred, multiphase, sequential, mixed-methods trial that will evaluate the feasibility of running a definitive large-scale randomised controlled trial of a loaded self-managed exercise programme versus usual physiotherapy. Initially, 8–10 participants with a minimum 3-month history of PFP will be recruited from an NHS physiotherapy waiting list and interviewed. Participants will be invited to discuss perceived barriers and facilitators to exercise engagement, and the meaning and impact of PFP. Then, 60 participants will be recruited in the same manner for the main phase of the feasibility trial. A web-based service will randomise patients to a loaded self-managed exercise programme or usual physiotherapy. The loaded self-managed exercise programme is aimed at addressing lower limb knee and hip weakness and is positioned within a framework of reducing fear/avoidance with an emphasis on self-management. Baseline assessment will include demographic data, average pain within the last week (VAS), fear avoidance behaviours, catastrophising, self-efficacy, sport and leisure activity participation, and general quality of life. Follow-up will be 3 and 6 months. The analysis will focus on descriptive statistics and confidence intervals. The qualitative components will follow a thematic analysis approach. Discussion: This study will evaluate the feasibility of running a definitive large-scale trial on patients with patellofemoral pain, within the NHS in the UK. We will identify strengths and weaknesses of the proposed protocol and the utility and characteristics of the outcome measures. The results from this study will inform the design of a multicentre trial