When the heart rules the head: ischaemic stroke and intracerebral haemorrhage complicating infective endocarditis

Sir William Osler meticulously described the clinical manifestations of infective endocarditis in 1885, concluding that: 'few diseases present greater difficulties in the way of diagnosis … which in many cases are practically insurmountable'. Even with modern investigation techniques, diagnosing infective endocarditis can be hugely challenging, yet is critically important in patients presenting with stroke (both cerebral infarction and intracranial haemorrhage), its commonest neurological complication. In ischaemic stroke, intravenous thrombolysis carries an unacceptably high risk of intracranial haemorrhage, while in intracerebral haemorrhage, mycotic aneurysms require urgent treatment to avoid rebleeding, and in all cases, prompt treatment with antibiotics and valve surgery may be life-saving. Here, we describe typical presentations of ischaemic stroke and intracerebral haemorrhage caused by infective endocarditis. We review the diagnostic challenges, the importance of rapid diagnosis, treatment options and controversies

A novel role for Lyl1 in primitive erythropoiesis

© 2018. Published by The Company of Biologists Ltd. Stem cell leukemia (Scl or Tal1) and lymphoblastic leukemia 1 (Lyl1) encode highly related members of the basic helix-loop-helix family of transcription factors that are co-expressed in the erythroid lineage. Previous studies have suggested that Scl is essential for primitive erythropoiesis. However, analysis of single-cell RNA-seq data of early embryos showed that primitive erythroid cells express both Scl and Lyl1. Therefore, to determine whether Lyl1 can function in primitive erythropoiesis, we crossed conditional Scl knockout mice with mice expressing a Cre recombinase under the control of the Epo receptor, active in erythroid progenitors. Embryos with 20% expression of Scl from E9.5 survived to adulthood. However, mice with reduced expression of Scl and absence of Lyl1 (double knockout; DKO) died at E10.5 because of progressive loss of erythropoiesis. Gene expression profiling of DKO yolk sacs revealed loss of Gata1 and many of the known target genes of the SCL-GATA1 complex. ChIP-seq analyses in a human erythroleukemia cell line showed that LYL1 exclusively bound a small subset of SCL targets including GATA1. Together, these data show for the first time that Lyl1 can maintain primitive erythropoiesis

Nested Case–Control Study of Autoimmune Disease in an Asbestos-Exposed Population

OBJECTIVE: To explore the potential association between asbestos exposure and risk of autoimmune disease, we conducted a case–control study among a cohort of 7,307 current and former residents of Libby, Montana, a community with historical occupational and environmental exposure to asbestos-contaminated vermiculite. METHODS: Cases were defined as those who reported having one of three systemic autoimmune diseases (SAIDs): systemic lupus erythematosus, scleroderma, or rheumatoid arthritis (RA). Controls were randomly selected at a 3:1 ratio from among the remaining 6,813 screening participants using frequency-matched age and sex groupings. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs) for SAIDs among those ≥ 65 years of age who had worked for the vermiculite mining company were 2.14 (95% CI, 0.90–5.10) for all SAIDs and 3.23 (95% CI, 1.31–7.96) for RA. In this age group, exposure to asbestos while in the military was also an independent risk factor, resulting in a tripling in risk. Other measures of occupational exposure to vermiculite indicated 54% and 65% increased risk for SAIDs and RA, respectively. Those who had reported frequent contact with vermiculite through various exposure pathways also demonstrated elevated risk for SAIDs and RA. We found increasing risk estimates for SAIDs with increasing numbers of reported vermiculite exposure pathways (p < 0.001). CONCLUSION: These preliminary findings support the hypothesis that asbestos exposure is associated with autoimmune disease. Refined measurements of asbestos exposure and SAID status among this cohort will help to further clarify the relationship between these variables

Foraging Behavior under Starvation Conditions Is Altered via Photosynthesis by the Marine Gastropod, Elysia clarki

It has been well documented that nutritional state can influence the foraging behavior of animals. However, photosynthetic animals, those capable of both heterotrophy and symbiotic photosynthesis, may have a delayed behavioral response due to their ability to photosynthesize. To test this hypothesis we subjected groups of the kleptoplastic sea slug, Elysia clarki, to a gradient of starvation treatments of 4, 8, and 12 weeks plus a satiated control. Compared to the control group, slugs starved 8 and 12 weeks displayed a significant increase in the proportion of slugs feeding and a significant decrease in photosynthetic capability, as measured in maximum quantum yield and [chl a]. The 4 week group, however, showed no significant difference in feeding behavior or in the metrics of photosynthesis compared to the control. This suggests that photosynthesis in E. clarki, thought to be linked to horizontally-transferred algal genes, delays a behavioral response to starvation. This is the first demonstration of a link between photosynthetic capability in an animal and a modification of foraging behavior under conditions of starvation

Spatially Explicit Data: Stewardship and Ethical Challenges in Science

Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration

HPV-Related Nonkeratinizing Squamous Cell Carcinoma of the Oropharynx: Utility of Microscopic Features in Predicting Patient Outcome

Human papilloma virus (HPV) is an etiologic agent in a subset of oropharyngeal squamous cell carcinomas (SCCs). The aim of this study was to sub-classify SCC of the oropharynx based upon histologic features into nonkeratinizing (NK) SCC, keratinizing (K) SCC, and hybrid SCC, and determine the frequency of HPV and patient survival in each group. Patients with oropharyngeal SCC with a minimum of 2 years of clinical follow-up were identified from radiation oncology databases from 1997 to 2004. All patients received either up front surgery with postoperative radiation or definitive radiation based therapy. In situ hybridization (ISH) for high-risk HPV subtypes and immunohistochemistry for p16, a protein frequently up-regulated in HPV-associated carcinomas, were performed. Overall and disease-specific survival were assessed. Of 118 cases, 46.6% were NK SCC, 24.6% K SCC and 28.8% hybrid SCC. NK SCC occurred in slightly younger patients that were more often male. It more frequently presented with lymph node metastases and was surgically resected compared to K SCC. NK SCC was significantly more likely to be HPV and p16 positive than KSCC (P < 0.001) and to have better overall and disease-specific survival (P = 0.0002; P = 0.0142, respectively). Hybrid SCC was also more likely than K SCC to be HPV and p16 positive (P = 0.003; P = 0.002, respectively) and to have better overall survival (P = 0.0105). Sub-classification of oropharyngeal SCC by histologic type provides useful clinical information. NK SCC histology strongly predicts HPV-association and better patient survival compared to K SCC. Hybrid SCC appears to have an intermediate frequency of HPV-association and patient survival

Nonlinear vortex light beams supported and stabilized by dissipation

We describe nonlinear Bessel vortex beams as localized and stationary solutions with embedded vorticity to the nonlinear Schr\"odinger equation with a dissipative term that accounts for the multi-photon absorption processes taking place at high enough powers in common optical media. In these beams, power and orbital angular momentum are permanently transferred to matter in the inner, nonlinear rings, at the same time that they are refueled by spiral inward currents of energy and angular momentum coming from the outer linear rings, acting as an intrinsic reservoir. Unlike vortex solitons and dissipative vortex solitons, the existence of these vortex beams does not critically depend on the precise form of the dispersive nonlinearities, as Kerr self-focusing or self-defocusing, and do not require a balancing gain. They have been shown to play a prominent role in "tubular" filamentation experiments with powerful, vortex-carrying Bessel beams, where they act as attractors in the beam propagation dynamics. Nonlinear Bessel vortex beams provide indeed a new solution to the problem of the stable propagation of ring-shaped vortex light beams in homogeneous self-focusing Kerr media. A stability analysis demonstrates that there exist nonlinear Bessel vortex beams with single or multiple vorticity that are stable against azimuthal breakup and collapse, and that the mechanism that renders these vortexes stable is dissipation. The stability properties of nonlinear Bessel vortex beams explain the experimental observations in the tubular filamentation experiments.Comment: Chapter of boo

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

Hiding from the Moonlight: Luminosity and Temperature Affect Activity of Asian Nocturnal Primates in a Highly Seasonal Forest

The effect of moonlight and temperature on activity of slow lorises was previously little known and this knowledge might be useful for understanding many aspects of their behavioural ecology, and developing strategies to monitor and protect populations. In this study we aimed to determine if the activity of the pygmy loris (Nycticebus pygmaeus) is affected by ambient temperature and/or moonlight in a mixed deciduous forest. We radio-collared five females and five males in the Seima Protection Forest, Cambodia, in February to May, 2008 and January to March, 2009 and recorded their behaviour at 5 minutes intervals, totalling 2736 observations. We classified each observation as either inactive (sleeping or alert) or active behaviour (travel, feeding, grooming, or others). Moon luminosity (bright/dark) and ambient temperature were recorded for each observation. The response variable, activity, was binary (active or inactive), and a logit link function was used. Ambient temperature alone did not significantly affect mean activity. Although mean activity was significantly affected by moonlight, the interaction between moonlight and temperature was also significant: on bright nights, studied animals were increasingly more active with higher temperature; and on dark nights they were consistently active regardless of temperature. The most plausible explanation is that on bright cold nights the combined risk of being seen and attacked by predators and heat loss outweigh the benefit of active behaviours