Mucosa-associated lymphoid tissue lymphoma and concurrent adenocarcinoma of the prostate

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is a rare disease that characteristically follows an indolent course. It is believed that infection or chronic inflammation may be triggers for malignant transformation in the prostate, but it is of unknown etiology. Reports of MALT lymphomas of the prostate with other concurrent primary prostate cancers are even more limited. We present the unique case of a 67-year-old male with concurrent adenocarcinoma of the prostate and primary MALT lymphoma of the prostate. The patient was treated with standard therapy for prostate adenocarcinoma, which would also treat a primary MALT lymphoma. He has been disease-free for over one year for both his primary malignancies. This case confirms that MALT lymphoma can arise concurrently with adenocarcinoma of the prostate

Text Mining the History of Medicine

Historical text archives constitute a rich and diverse source of information, which is becoming increasingly readily accessible, due to large-scale digitisation efforts. However, it can be difficult for researchers to explore and search such large volumes of data in an efficient manner. Text mining (TM) methods can help, through their ability to recognise various types of semantic information automatically, e.g., instances of concepts (places, medical conditions, drugs, etc.), synonyms/variant forms of concepts, and relationships holding between concepts (which drugs are used to treat which medical conditions, etc.). TM analysis allows search systems to incorporate functionality such as automatic suggestions of synonyms of user-entered query terms, exploration of different concepts mentioned within search results or isolation of documents in which concepts are related in specific ways. However, applying TM methods to historical text can be challenging, according to differences and evolutions in vocabulary, terminology, language structure and style, compared to more modern text. In this article, we present our efforts to overcome the various challenges faced in the semantic analysis of published historical medical text dating back to the mid 19th century. Firstly, we used evidence from diverse historical medical documents from different periods to develop new resources that provide accounts of the multiple, evolving ways in which concepts, their variants and relationships amongst them may be expressed. These resources were employed to support the development of a modular processing pipeline of TM tools for the robust detection of semantic information in historical medical documents with varying characteristics. We applied the pipeline to two large-scale medical document archives covering wide temporal ranges as the basis for the development of a publicly accessible semantically-oriented search system. The novel resources are available for research purposes, while the processing pipeline and its modules may be used and configured within the Argo TM platform

Optimisation of Over-Expression in E. coli and Biophysical Characterisation of Human Membrane Protein Synaptogyrin 1

Progress in functional and structural studies of integral membrane proteins (IMPs) is lacking behind their soluble counterparts due to the great challenge in producing stable and homogeneous IMPs. Low natural abundance, toxicity when over-expressed and potential lipid requirements of IMPs are only a few reasons for the limited progress. Here, we describe an optimised workflow for the recombinant over-expression of the human tetraspan vesicle protein (TVP) synaptogyrin in Escherichia coli and its biophysical characterisation. TVPs are ubiquitous and abundant components of vesicles. They are believed to be involved in various aspects of the synaptic vesicle cycle, including vesicle biogenesis, exocytosis and endocytotic recycling. Even though TVPs are found in most cell types, high-resolution structural information for this class of membrane proteins is still missing. The optimisation of the N-terminal sequence of the gene together with the usage of the recently developed Lemo21(DE3) strain which allows the balancing of the translation with the membrane insertion rate led to a 50-fold increased expression rate compared to the classical BL21(DE3) strain. The protein was soluble and stable in a variety of mild detergents and multiple biophysical methods confirmed the folded state of the protein. Crosslinking experiments suggest an oligomeric architecture of at least four subunits. The protein stability is significantly improved in the presence of cholesteryl hemisuccinate as judged by differential light scattering. The approach described here can easily be adapted to other eukaryotic IMPs

Resolving the Evolutionary History of Campanula (Campanulaceae) in Western North America

Recent phylogenetic works have begun to address long-standing questions regarding the systematics of Campanula (Campanulaceae). Yet, aspects of the evolutionary history, particularly in northwestern North America, remain unresolved. Thus, our primary goal in this study was to infer the phylogenetic positions of northwestern Campanula species within the greater Campanuloideae tree. We combined new sequence data from 5 markers (atpB, rbcL, matK, and trnL-F regions of the chloroplast and the nuclear ITS) representing 12 species of Campanula with previously published datasets for worldwide campanuloids, allowing us to include approximately 75% of North American Campanuleae in a phylogenetic analysis of the Campanuloideae. Because all but one of North American Campanula species are nested within a single campanuloid subclade (the Rapunculus clade), we conducted a separate set of analyses focused specifically on this group. Our findings show that i) the campanuloids have colonized North America at least 6 times, 4 of which led to radiations, ii) all but one North American campanuloid are nested within the Rapunculus clade, iii) in northwestern North America, a C. piperi – C. lasiocarpa ancestor gave rise to a monophyletic Cordilleran clade that is sister to a clade containing C. rotundifolia, iv) within the Cordilleran clade, C. parryi var. parryi and C. parryi var. idahoensis exhibit a deep, species-level genetic divergence, and v) C. rotundifolia is genetically diverse across its range and polyphyletic. Potential causes of diversification and endemism in northwestern North America are discussed

Widespread Contribution of Gdf7 Lineage to Cerebellar Cell Types and Implications for Hedgehog-Driven Medulloblastoma Formation

The roof plate is a specialized embryonic midline tissue of the central nervous system that functions as a signaling center regulating dorsal neural patterning. In the developing hindbrain, roof plate cells express Gdf7 and previous genetic fate mapping studies showed that these cells contribute mostly to non-neural choroid plexus epithelium. We demonstrate here that constitutive activation of the Sonic hedgehog signaling pathway in the Gdf7 lineage invariably leads to medulloblastoma. Lineage tracing analysis reveals that Gdf7-lineage cells not only are a source of choroid plexus epithelial cells, but are also present in the cerebellar rhombic lip and contribute to a subset of cerebellar granule neuron precursors, the presumed cell-of-origin for Sonic hedgehog-driven medulloblastoma. We further show that Gdf7-lineage cells also contribute to multiple neuronal and glial cell types in the cerebellum, including glutamatergic granule neurons, unipolar brush cells, Purkinje neurons, GABAergic interneurons, Bergmann glial cells, and white matter astrocytes. These findings establish hindbrain roof plate as a novel source of diverse neural cell types in the cerebellum that is also susceptible to oncogenic transformation by deregulated Sonic hedgehog signaling

Target 2035-update on the quest for a probe for every protein

Twenty years after the publication of the first draft of the human genome, our knowledge of the human proteome is still fragmented. The challenge of translating the wealth of new knowledge from genomics into new medicines is that proteins, and not genes, are the primary executers of biological function. Therefore, much of how biology works in health and disease must be understood through the lens of protein function. Accordingly, a subset of human proteins has been at the heart of research interests of scientists over the centuries, and we have accumulated varying degrees of knowledge about approximately 65% of the human proteome. Nevertheless, a large proportion of proteins in the human proteome (∼35%) remains uncharacterized, and less than 5% of the human proteome has been successfully targeted for drug discovery. This highlights the profound disconnect between our abilities to obtain genetic information and subsequent development of effective medicines. Target 2035 is an international federation of biomedical scientists from the public and private sectors, which aims to address this gap by developing and applying new technologies to create by year 2035 chemogenomic libraries, chemical probes, and/or biological probes for the entire human proteome

OGLE-2019-BLG-0825: Constraints on the Source System and Effect on Binary-lens Parameters arising from a Five Day Xallarap Effect in a Candidate Planetary Microlensing Event

We present an analysis of microlensing event OGLE-2019-BLG-0825. This event was identified as a planetary candidate by preliminary modeling. We find that significant residuals from the best-fit static binary-lens model exist and a xallarap effect can fit the residuals very well and significantly improves $\chi^2$ values. On the other hand, by including the xallarap effect in our models, we find that binary-lens parameters like mass-ratio, $q$, and separation, $s$, cannot be constrained well. However, we also find that the parameters for the source system like the orbital period and semi major axis are consistent between all the models we analyzed. We therefore constrain the properties of the source system better than the properties of the lens system. The source system comprises a G-type main-sequence star orbited by a brown dwarf with a period of $P\sim5$ days. This analysis is the first to demonstrate that the xallarap effect does affect binary-lens parameters in planetary events. It would not be common for the presence or absence of the xallarap effect to affect lens parameters in events with long orbital periods of the source system or events with transits to caustics, but in other cases, such as this event, the xallarap effect can affect binary-lens parameters.Comment: 19 pages, 7 figures, 6 tables. Accepted by A

Examining the Relationships among Motivation, Service Quality and Loyalty: The case of the National Museum of Natural Science

This study explores causal relationships between push and pull motivations, perceptions of service quality and loyalty intention, and examines the moderating role of membership status in the National Museum of Natural Science, the largest museum in Taiwan. Data were collected from 405 paid admission visitors, with a quota and systematic sampling, from two stages of pre- and post-visit corresponding with two questionnaires. The results demonstrate that push and pull motivations impact on service quality perceptions, which in turn influence museum loyalty; the effect of pull motivation on service quality perceptions in the nonmember group was stronger than in the member group; the effect of service quality perceptions on loyalty in the member group was stronger than in the nonmember group. Museum managers could tailor and advertise existing museum products and services to different types of visitors; assuring the museum's continued operation and success