Imaging features of foreign body granuloma in the lower extremities mimicking a soft tissue neoplasm

Foreign body granuloma is a tissue reaction for retained foreign bodies after skin-penetrating trauma. Detection of retained foreign bodies can be extremely difficult when the patients present with non-specific symptoms such as pain and/or swelling without recognizing a previous trauma. We report three patients of foreign body granulomas in the lower extremities with emphasis placed on their unique clinical and radiological features. The involved sites were the foot, posterior thigh, and posterior lower leg, with wooden splinters in two patients and a fragment of tile in one. Plain radiographs could not reveal the existence of foreign bodies. Magnetic resonance imaging (MRI) showed foreign bodies as low intensities on both T1- and T2-weighted images in two patients, and the surrounding reactive lesion as low to iso intensities on T1- and high intensities on T2-weighted images in all the patients. The peripheral areas of the lesion were strongly enhanced after gadolinium injection. Ultrasound sonography could clearly visualize a foreign body as an echogenic area with posterior acoustic shadowing in one patient. The surrounding ring-like reactive lesion is easily mistaken for a soft tissue neoplasm when foreign bodies are not identified. The key to arriving at the correct diagnosis is to clarify the previous trauma and to identify foreign bodies with low signal intensities on both T1- and T2-weighted images and/or the characteristic ring-like enhancement on MRI. It is also necessary to rule out a foreign body granuloma whenever we see patients with a soft tissue tumor in the extremities, irrespective of their previous trauma history

Prevalence of rheumatic heart disease in North-Central Nigeria: a school-based cross-sectional pilot study.

OBJECTIVES: To present epidemiological data on rheumatic heart disease (RHD), the most common acquired heart disease in children and young adults in low- and middle-income countries, for North-Central Nigeria. METHODS: In this pilot study, we conducted clinical and echocardiography screening on a cross section of randomly selected secondary schoolchildren in Jos, North-Central Nigeria, from March to September 2016. For outcome classification into borderline or definite RHD, we performed a confirmatory echocardiography using the World Heart Federation criteria for those suspected to have RHD from the screening. RESULTS: A total of 417 secondary schoolchildren were screened, of whom 247 (59.2%) were female. The median age was 14 years (IQR: 13-15). Clinical screening detected 8/417 children, whereas screening echocardiography detected 42/417 suspected cases of RHD. Definitive echocardiography confirmed 9/417 with RHD corresponding to a prevalence of 21.6 per 1000 (95% CI, 6.7-36.5). All but one of the confirmed RHD cases (8/9) were borderline RHD corresponding to a prevalence of 19.2 per 1000 (95% CI, 8.3-37.5) for borderline RHD and 2.4 per 1000 (95% CI, 0.1-13.3) for definite RHD. RHD was more common in boys and cardiac auscultation missed over 50% of the cases. CONCLUSIONS: This study showed a high prevalence of RHD among secondary schoolchildren in North-Central Nigeria with a vast predominance of asymptomatic borderline lesions. Larger school-based echocardiography screening using portable or handheld echocardiography aimed at early detection of subclinical RHD should be adopted

The Importance of Conserving Biodiversity Outside of Protected Areas in Mediterranean Ecosystems

Mediterranean-type ecosystems constitute one of the rarest terrestrial biomes and yet they are extraordinarily biodiverse. Home to over 250 million people, the five regions where these ecosystems are found have climate and coastal conditions that make them highly desirable human habitats. The current conservation landscape does not reflect the mediterranean biome's rarity and its importance for plant endemism. Habitat conversion will clearly outpace expansion of formal protected-area networks, and conservationists must augment this traditional strategy with new approaches to sustain the mediterranean biota. Using regional scale datasets, we determine the area of land in each of the five regions that is protected, converted (e.g., to urban or industrial), impacted (e.g., intensive, cultivated agriculture), or lands that we consider to have conservation potential. The latter are natural and semi-natural lands that are unprotected (e.g., private range lands) but sustain numerous native species and associated habitats. Chile has the greatest proportion of its land (75%) in this category and California-Mexico the least (48%). To illustrate the potential for achieving mediterranean biodiversity conservation on these lands, we use species-area curves generated from ecoregion scale data on native plant species richness and vertebrate species richness. For example, if biodiversity could be sustained on even 25% of existing unprotected, natural and semi-natural lands, we estimate that the habitat of more than 6,000 species could be represented. This analysis suggests that if unprotected natural and semi-natural lands are managed in a manner that allows for persistence of native species, we can realize significant additional biodiversity gains. Lasting biodiversity protection at the scale needed requires unprecedented collaboration among stakeholders to promote conservation both inside and outside of traditional protected areas, including on lands where people live and work

Innate Immune Suppression Enables Frequent Transfection with RNA Encoding Reprogramming Proteins

BACKGROUND: Generating autologous pluripotent stem cells for therapeutic applications will require the development of efficient DNA-free reprogramming techniques. Transfecting cells with in vitro-transcribed, protein-encoding RNA is a straightforward method of directly expressing high levels of reprogramming proteins without genetic modification. However, long-RNA transfection triggers a potent innate immune response characterized by growth inhibition and the production of inflammatory cytokines. As a result, repeated transfection with protein-encoding RNA causes cell death. METHODOLOGY/PRINCIPAL FINDINGS: RNA viruses have evolved methods of disrupting innate immune signaling by destroying or inhibiting specific proteins to enable persistent infection. Starting from a list of known viral targets, we performed a combinatorial screen to identify siRNA cocktails that could desensitize cells to exogenous RNA. We show that combined knockdown of interferon-beta (Ifnb1), Eif2ak2, and Stat2 rescues cells from the innate immune response triggered by frequent long-RNA transfection. Using this technique, we were able to transfect primary human fibroblasts every 24 hours with RNA encoding the reprogramming proteins Oct4, Sox2, Klf4, and Utf1. We provide evidence that the encoded protein is active, and we show that expression can be maintained for many days, through multiple rounds of cell division. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that suppressing innate immunity enables frequent transfection with protein-encoding RNA. This technique represents a versatile tool for investigating expression dynamics and protein interactions by enabling precise control over levels and timing of protein expression. Our finding also opens the door for the development of reprogramming and directed-differentiation methods based on long-RNA transfection

Calcium modulates force sensing by the von Willebrand factor A2 domain

von Willebrand factor (VWF) multimers mediate primary adhesion and aggregation of platelets. VWF potency critically depends on multimer size, which is regulated by a feedback mechanism involving shear-induced unfolding of the VWF-A2 domain and cleavage by the metalloprotease ADAMTS-13. Here we report crystallographic and single-molecule optical tweezers data on VWF-A2 providing mechanistic insight into calcium-mediated stabilization of the native conformation that protects A2 from cleavage by ADAMTS-13. Unfolding of A2 requires higher forces when calcium is present and primarily proceeds through a mechanically stable intermediate with non-native calcium coordination. Calcium further accelerates refolding markedly, in particular, under applied load. We propose that calcium improves force sensing by allowing reversible force switching under physiologically relevant hydrodynamic conditions. Our data show for the first time the relevance of metal coordination for mechanical properties of a protein involved in mechanosensing

Insights into deposition of Lower Cretaceous black shales from meager accumulation of organic matter in Albian sediments from ODP site 763, Exmouth Plateau, Northwest Australia

The amount and type of organic matter present in an exceptionally complete upper Aptian to lower Cenomanian sequence of sediments from ODP site 763 on the Exmouth Plateau has been determined. Organic carbon concentrations average 0.2%. Organic matter is marine in origin, and its production and preservation was low over the ca. 20-million-year interval recorded by this sequence. Because this section was tectonically isolated from mainland Australia in the early Aptian, it better represents global oceanic conditions than the many basin-edge locations in which Albian-age black shales have been found. Formation of the basin-edge black shales evidently resulted from rapid, turbiditic burial of organic matter rather than from enhanced oceanic production or from basin-wide anoxia during the Albian.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47134/1/367_2005_Article_BF02202605.pd

Nuclear Scaffold Attachment Sites within ENCODE Regions Associate with Actively Transcribed Genes

The human genome must be packaged and organized in a functional manner for the regulation of DNA replication and transcription. The nuclear scaffold/matrix, consisting of structural and functional nuclear proteins, remains after extraction of nuclei and anchors loops of DNA. In the search for cis-elements functioning as chromatin domain boundaries, we identified 453 nuclear scaffold attachment sites purified by lithium-3,5-iodosalicylate extraction of HeLa nuclei across 30 Mb of the human genome studied by the ENCODE pilot project. The scaffold attachment sites mapped predominately near expressed genes and localized near transcription start sites and the ends of genes but not to boundary elements. In addition, these regions were enriched for RNA polymerase II and transcription factor binding sites and were located in early replicating regions of the genome. We believe these sites correspond to genome-interactions mediated by transcription factors and transcriptional machinery immobilized on a nuclear substructure

A novel potent tumour promoter aberrantly overexpressed in most human cancers

The complexity and heterogeneity of tumours have hindered efforts to identify commonalities among different cancers. Furthermore, because we have limited information on the prevalence and nature of ubiquitous molecular events that occur in neoplasms, it is unfeasible to implement molecular-targeted cancer screening and prevention. Here, we found that the FEAT protein is overexpressed in most human cancers, but weakly expressed in normal tissues including the testis, brain, and liver. Transgenic mice that ectopically expressed FEAT in the thymus, spleen, liver, and lung spontaneously developed invasive malignant lymphoma (48%, 19/40) and lung-metastasizing liver cancer (hepatocellular carcinoma) (35%, 14/40) that models human hepatocarcinogenesis, indicating the FEAT protein potently drives tumorigenesis in vivo. Gene expression profiling suggested that FEAT drives receptor tyrosine kinase and hedgehog signalling pathways. These findings demonstrate that integrated efforts to identify FEAT-like ubiquitous oncoproteins are useful and may provide promising approaches for cost-effective cancer screening and prevention

Changes in Dynamics upon Oligomerization Regulate Substrate Binding and Allostery in Amino Acid Kinase Family Members

Oligomerization is a functional requirement for many proteins. The interfacial interactions and the overall packing geometry of the individual monomers are viewed as important determinants of the thermodynamic stability and allosteric regulation of oligomers. The present study focuses on the role of the interfacial interactions and overall contact topology in the dynamic features acquired in the oligomeric state. To this aim, the collective dynamics of enzymes belonging to the amino acid kinase family both in dimeric and hexameric forms are examined by means of an elastic network model, and the softest collective motions (i.e., lowest frequency or global modes of motions) favored by the overall architecture are analyzed. Notably, the lowest-frequency modes accessible to the individual subunits in the absence of multimerization are conserved to a large extent in the oligomer, suggesting that the oligomer takes advantage of the intrinsic dynamics of the individual monomers. At the same time, oligomerization stiffens the interfacial regions of the monomers and confers new cooperative modes that exploit the rigid-body translational and rotational degrees of freedom of the intact monomers. The present study sheds light on the mechanism of cooperative inhibition of hexameric N-acetyl-L-glutamate kinase by arginine and on the allosteric regulation of UMP kinases. It also highlights the significance of the particular quaternary design in selectively determining the oligomer dynamics congruent with required ligand-binding and allosteric activities