An unusual case of metastasis to the left side of the heart: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cardiac metastases are found in six to 20% of autopsies of patients with malignant neoplasm. The most common neoplasms that metastasize to the heart are malignant melanoma, lymphoma, and leukemia, but the relative numbers are greater with breast and lung cancers, reflecting the most common incidence of these cancers.</p> <p>Case presentation</p> <p>A 60-year-old Hispanic man presented to our hospital after being transferred from an outside hospital for workup and evaluation of an adrenal mass of the abdomen and pelvis, found on computed tomography. His chief complaint upon admission was altered mental status. Physical examination was unremarkable. He was alert and oriented and had a dry and non-erythematous oropharynx, and bilateral diffuse wheezing on lung examination. Computed tomography of the chest showed multiple hypodense lesions in the left ventricular myocardium, suggestive of metastases. There were also tiny sub-centimeter nodular densities in the right upper and lower lobes. Adrenal glands contained hypodense lesions, which showed characteristic adenocarcinomatous malignant cells.</p> <p>Conclusion</p> <p>Cancers which have metastasized to the heart are found in six to 20% of patients with malignant neoplasms. The right side of the heart is more commonly involved in metastasis. This study is unusual in that a tumor of an unknown primary origin had metastasized to the left side of the heart.</p

Three dimensional first-pass myocardial perfusion imaging at 3T: feasibility study

<p>Abstract</p> <p>Background</p> <p>In patients with ischemic heart disease, accurate assessment of the extent of myocardial perfusion deficit may be important in predicting prognosis of clinical cardiac outcomes. The aim of this study was to compare the ability of three dimensional (3D) and of two dimensional (2D) multi-slice myocardial perfusion imaging (MPI) using cardiovascular magnetic resonance (CMR) in determining the size of defects, and to demonstrate the feasibility of 3D MPI in healthy volunteers at 3 Tesla.</p> <p>Methods</p> <p>A heart phantom was used to compare the accuracy of 3D and 2D multi-slice MPI in estimating the volume fraction of seven rubber insets which simulated transmural myocardial perfusion defects. Three sets of cross-sectional planes were acquired for 2D multi-slice imaging, where each set was shifted along the partition encoding direction by ± 10 mm. 3D first-pass contrast-enhanced (0.1 mmol/kg Gd-DTPA) MPI was performed in three volunteers with sensitivity encoding for six-fold acceleration. The upslope of the myocardial time-intensity-curve and peak SNR/CNR values were calculated.</p> <p>Results</p> <p>Mean/standard deviation of errors in estimating the volume fraction across the seven defects were -0.44/1.49%, 2.23/2.97%, and 2.59/3.18% in 3D, 2D 4-slice, and 2D 3-slice imaging, respectively. 3D MPI performed in healthy volunteers produced excellent quality images with whole left ventricular (LV) coverage. Peak SNR/CNR was 57.6 ± 22.0/37.5 ± 19.7 over all segments in the first eight slices.</p> <p>Conclusion</p> <p>3D performed better than 2D multi-slice MPI in estimating the size of perfusion defects in phantoms. Highly accelerated 3D MPI at 3T was feasible in volunteers, allowing whole LV coverage with excellent image quality and high SNR/CNR.</p

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Differential expression of a BMP4 reporter allele in anterior fungiform versus posterior circumvallate taste buds of mice

<p>Abstract</p> <p>Background</p> <p>Bone Morphogenetic Protein 4 (BMP4) is a diffusible factor which regulates embryonic taste organ development. However, the role of BMP4 in taste buds of adult mice is unknown. We utilized transgenic mice with LacZ under the control of the BMP4 promoter to reveal the expression of BMP4 in the tongues of adult mice. Further we evaluate the pattern of BMP4 expression with that of markers of specific taste bud cell types and cell proliferation to define and compare the cell populations expressing BMP4 in anterior (fungiform papillae) and posterior (circumvallate papilla) tongue.</p> <p>Results</p> <p>BMP4 is expressed in adult fungiform and circumvallate papillae, i.e., lingual structures composed of non-taste epithelium and taste buds. Unexpectedly, we find both differences and similarities with respect to expression of BMP4-driven ß-galactosidase. In circumvallate papillae, many fusiform cells within taste buds are BMP4-ß-gal positive. Further, a low percentage of BMP4-expressing cells within circumvallate taste buds is immunopositive for markers of each of the three differentiated taste cell types (I, II and III). BMP4-positive intragemmal cells also expressed a putative marker of immature taste cells, Sox2, and consistent with this finding, intragemmal cells expressed BMP4-ß-gal within 24 hours after their final mitosis, as determined by BrdU birthdating. By contrast, in fungiform papillae, BMP4-ß-gal positive cells are never encountered within taste buds. However, in both circumvallate and fungiform papillae, BMP4-ß-gal expressing cells are located in the perigemmal region, comprising basal and edge epithelial cells adjacent to taste buds proper. This region houses the proliferative cell population that gives rise to adult taste cells. However, perigemmal BMP4-ß-gal cells appear mitotically silent in both fungiform and circumvallate taste papillae, as we do not find evidence of their active proliferation using cell cycle immunomarkers and BrdU birthdating.</p> <p>Conclusion</p> <p>Our data suggest that intragemmal BMP4-ß-gal cells in circumvallate papillae are immature taste cells which eventually differentiate into each of the 3 taste cell types, whereas perigemmal BMP4-ß-gal cells in both circumvallate and fungiform papillae may be slow cycling stem cells, or belong to the stem cell niche to regulate taste cell renewal from the proliferative cell population.</p

Proteolysis-Dependent Remodeling of the Tubulin Homolog FtsZ at the Division Septum in \u3ci\u3eEscherichia coli\u3c/i\u3e

During bacterial cell division a dynamic protein structure called the Z-ring assembles at the septum. The major protein in the Z-ring in Escherichia coli is FtsZ, a tubulin homolog that polymerizes with GTP. FtsZ is degraded by the two-component ATP-dependent protease ClpXP. Two regions of FtsZ, located outside of the polymerization domain in the unstructured linker and at the C-terminus, are important for specific recognition and degradation by ClpXP. We engineered a synthetic substrate containing green fluorescent protein (Gfp) fused to an extended FtsZ C-terminal tail (residues 317–383), including the unstructured linker and the C-terminal conserved region, but not the polymerization domain, and showed that it is sufficient to target a non-native substrate for degradation in vitro. To determine if FtsZ degradation regulates Z-ring assembly during division, we expressed a full length Gfp-FtsZ fusion protein in wild type and clp deficient strains and monitored fluorescent Z-rings. In cells deleted for clpX or clpP, or cells expressing protease-defective mutant protein ClpP(S97A), Z-rings appear normal; however, after photobleaching a region of the Z-ring, fluorescence recovers ~70% more slowly in cells without functional ClpXP than in wild type cells. Gfp-FtsZ(R379E), which is defective for degradation by ClpXP, also assembles into Z-rings that recover fluorescence ~2-fold more slowly than Z-rings containing Gfp-FtsZ. In vitro, ClpXP cooperatively degrades and disassembles FtsZ polymers. These results demonstrate that ClpXP is a regulator of Z-ring dynamics and that the regulation is proteolysis-dependent. Our results further show that FtsZ-interacting proteins in E. coli fine-tune Z-ring dynamics

Stakeholder views on secondary findings in whole-genome and whole-exome sequencing:a systematic review of quantitative and qualitative studies

Purpose: As whole-exome and whole-genome sequencing (WES/WGS) move into routine clinical practice, it is timely to review data that might inform the debate around secondary findings (SF) and the development of policies that maximize participant benefit. Methods: We systematically searched for qualitative and quantitative studies that explored stakeholder views on SF in WES/WGS. Framework analysis was undertaken to identify major themes. Results: 44 articles reporting the views of 11,566 stakeholders were included. Stakeholders were broadly supportive of returning ‘actionable’ findings, but definitions of actionability varied. Stakeholder views on SF disclosure exist along a spectrum: potential WES/WGS recipients’ views were largely influenced by a sense of rights, while views of genomics professionals were informed by a sense of professional responsibility. Experience of genetic illness and testing resulted in greater caution about SF, suggesting that truly informed decisions require an understanding of the implications and limitations of WES/WGS and possible findings. Conclusion: This review suggests that bidirectional interaction during consent might best facilitate informed decision-making about SF, and that dynamic forms of consent, allowing for changing preferences, should be considered. Research exploring views from wider perspectives and from recipients who have received SF is critical if evidence-based policies are to be achieved.</p

In Vivo Structure of the E. coli FtsZ-ring Revealed by Photoactivated Localization Microscopy (PALM)

The FtsZ protein, a tubulin-like GTPase, plays a pivotal role in prokaryotic cell division. In vivo it localizes to the midcell and assembles into a ring-like structure-the Z-ring. The Z-ring serves as an essential scaffold to recruit all other division proteins and generates contractile force for cytokinesis, but its supramolecular structure remains unknown. Electron microscopy (EM) has been unsuccessful in detecting the Z-ring due to the dense cytoplasm of bacterial cells, and conventional fluorescence light microscopy (FLM) has only provided images with limited spatial resolution (200–300 nm) due to the diffraction of light. Hence, given the small sizes of bacteria cells, identifying the in vivo structure of the Z-ring presents a substantial challenge. Here, we used photoactivated localization microscopy (PALM), a single molecule-based super-resolution imaging technique, to characterize the in vivo structure of the Z-ring in E. coli. We achieved a spatial resolution of ∼35 nm and discovered that in addition to the expected ring-like conformation, the Z-ring of E. coli adopts a novel compressed helical conformation with variable helical length and pitch. We measured the thickness of the Z-ring to be ∼110 nm and the packing density of FtsZ molecules inside the Z-ring to be greater than what is expected for a single-layered flat ribbon configuration. Our results strongly suggest that the Z-ring is composed of a loose bundle of FtsZ protofilaments that randomly overlap with each other in both longitudinal and radial directions of the cell. Our results provide significant insight into the spatial organization of the Z-ring and open the door for further investigations of structure-function relationships and cell cycle-dependent regulation of the Z-ring

Escherichia coli MazF Leads to the Simultaneous Selective Synthesis of Both “Death Proteins” and “Survival Proteins”

The Escherichia coli mazEF module is one of the most thoroughly studied toxin–antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. MazF is an endoribonuclease that leads to the inhibition of protein synthesis by cleaving mRNAs at ACA sequences. Here, using 2D-gels, we show that in E. coli, although MazF induction leads to the inhibition of the synthesis of most proteins, the synthesis of an exclusive group of proteins, mostly smaller than about 20 kDa, is still permitted. We identified some of those small proteins by mass spectrometry. By deleting the genes encoding those proteins from the E. coli chromosome, we showed that they were required for the death of most of the cellular population. Under the same experimental conditions, which induce mazEF-mediated cell death, other such proteins were found to be required for the survival of a small sub-population of cells. Thus, MazF appears to be a regulator that induces downstream pathways leading to death of most of the population and the continued survival of a small sub-population, which will likely become the nucleus of a new population when growth conditions become less stressful

Reading Speed, Comprehension and Eye Movements While Reading Japanese Novels: Evidence from Untrained Readers and Cases of Speed-Reading Trainees

BACKGROUND: A growing body of evidence suggests that meditative training enhances perception and cognition. In Japan, the Park-Sasaki method of speed-reading involves organized visual training while forming both a relaxed and concentrated state of mind, as in meditation. The present study examined relationships between reading speed, sentence comprehension, and eye movements while reading short Japanese novels. In addition to normal untrained readers, three middle-level trainees and one high-level expert on this method were included for the two case studies. METHODOLOGY/PRINCIPAL FINDINGS: In Study 1, three of 17 participants were middle-level trainees on the speed-reading method. Immediately after reading each story once on a computer monitor, participants answered true or false questions regarding the content of the novel. Eye movements while reading were recorded using an eye-tracking system. Results revealed higher reading speed and lower comprehension scores in the trainees than in the untrained participants. Furthermore, eye-tracking data by untrained participants revealed multiple correlations between reading speed, accuracy and eye-movement measures, with faster readers showing shorter fixation durations and larger saccades in X than slower readers. In Study 2, participants included a high-level expert and 14 untrained students. The expert showed higher reading speed and statistically comparable, although numerically lower, comprehension scores compared with the untrained participants. During test sessions this expert moved her eyes along a nearly straight horizontal line as a first pass, without moving her eyes over the whole sentence display as did the untrained students. CONCLUSIONS/SIGNIFICANCE: In addition to revealing correlations between speed, comprehension and eye movements in reading Japanese contemporary novels by untrained readers, we describe cases of speed-reading trainees regarding relationships between these variables. The trainees overall tended to show poor performance influenced by the speed-accuracy trade-off, although this trade-off may be reduced in the case of at least one high-level expert

A discrete choice experiment of preferences for genetic counselling among Jewish women seeking cancer genetics services

To determine which aspects of breast cancer genetic counselling are important to Ashkenazi Jewish women, a discrete choice experiment was conducted. Participants consisted of 339 Australian Ashkenazi Jewish women who provided a blood sample for research used to test for Ashkenazi Jewish ancestral mutations in the genes BRCA1 and BRCA2, and were offered their genetic test result through a cancer genetics service. Main outcome measures were women's preferences for, and trade-offs between, the genetic counselling aspects of providing cancer, gene, and risk information (information); giving advice about cancer surveillance (surveillance); preparing for genetic testing (preparation); and, assistance with decision-making (direction). Respondents most valued information, about twice as much as advice about surveillance, four times as much as preparation for testing, and nine times as much as assistance with decision-making, which was least valued. Women's preferences were consistent with the major goals of genetic counselling, which include providing information and surveillance advice, and avoiding direction by facilitating autonomous decision-making. There were differences between the women in which aspects they most favoured, suggesting that counselling that elicits and responds to clients' preferences is more likely to meet clients' needs