julilili42/papers huggingface dataset:
Evolution of Arabidopsis thaliana microRNAs from random sequences
2008-10-24

One mechanism for the origin of new plant microRNAs (miRNAs) is from inverted duplications of transcribed genes. However, even though many young MIRNA genes have recently been identified in Arabidopsis thaliana , only a subset shows evidence for having evolved by this route. We propose that the hundreds of thousands of partially self-complementary foldback sequences found in a typical plant genome provide an alternative path for miRNA evolution. Our genome-wide analyses of young MIRNA genes suggest that some arose from DNA that either has self-complementarity by chance or that represents a highly eroded inverted duplication. These observations are compatible with the idea that, following capture of transcriptional regulatory sequences, random foldbacks can occasionally spawn new miRNAs. Subsequent stabilization through coevolution with initially fortuitous targets may lead to fixation of a small subset of these proto-miRNA genes.
New Insights Into Mid‐Late Pleistocene Fossil Hominin Paranasal Sinus Morphology
2008-10-24

Abstract Mid‐late Pleistocene fossil hominins such as Homo neanderthalensis and H. heidelbergensis are often described as having extensively pneumatized crania compared with modern humans. However, the significance of pneumatization in recognizing patterns of phyletic diversification and/or functional specialization has remained controversial. Here, we test the null hypothesis that the paranasal sinuses of fossil and extant humans and great apes can be understood as biological spandrels, i.e., their morphology reflects evolutionary, developmental, and functional constraints imposed onto the surrounding bones. Morphological description of well‐preserved mid‐late Pleistocene hominin specimens are contrasted with our comparative sample of modern humans and great apes. Results from a geometric morphometric analysis of the correlation between paranasal sinus and cranial dimensions show that the spandrel hypothesis cannot be refuted. However, visualizing specific features of the paranasal sinus system with methods of biomedical imaging and computer graphics reveals new aspects of patterns of growth and development of fossil hominins. Anat Rec, 291:1506–1516, 2008. © 2008 Wiley‐Liss, Inc.
Decreased Plasma and Cerebrospinal Fluid Levels of Stem Cell Factor in Patients with Early Alzheimer's Disease
2008-10-24

Alzheimer's disease (AD) is characterized by massive neuronal cell loss in the brain. Stem cell factor (SCF) is a hematopoietic growth factor (HGF) that promotes neuroprotective effects and supports neurogenesis in the brain. In the present study, we found significantly lower SCF plasma levels in 30 early AD patients (908.5 +/- 181.7 pg/ml) in comparison with 30 age-matched healthy controls (1058.3 +/- 221.5 pg/ml; p = 0.006). SCF plasma levels in AD patients showed a significant inverse correlation with dementia severity as measured by ADAS-Cog (r = -0.289; p = 0.037). AD patients showed significantly lower SCF levels in cerebrospinal fluid (CSF) (131.60 +/- 43.03 pg/ml) in comparison with 15 age- and gender-matched patients with other non-inflammatory neurological disease (NIND) (166.03 +/- 42.5 pg/ml; p = 0.017). In addition, we found significant positive correlations between SCF and CXCL12 (also known as SDF-1) plasma levels in healthy controls (r = 0.341; p = 0.008) and between SCF and CXCL12 CSF levels in AD patients (r = 0.487; p < 0.001). In conclusion, decreased SCF plasma and CSF levels in early AD patients may contribute to a deficient hematopoietic brain support with putative pathogenic and clinical relevance. Further studies are needed to examine whether a manipulation of HGFs such as SCF could be a promising new therapeutic strategy for AD.
Wnt/β-catenin signaling controls development of the blood–brain barrier
2008-10-27

The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of β-cat in vivo enhances barrier maturation, whereas inactivation of β-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of β-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of β-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of β-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown.
Systematic Contact-Free 3D Topometry of the Soft Tissue Profile in Cleft Lips
2008-10-27

Objective: To evaluate the clinical application of three-dimensional (3D) imaging for the analysis of a broad variety of cleft lips and to conduct a systematic analysis. Design: This was a prospective study using a noncontact 3D laser scanner to acquire the preoperative 3D facial profiles. The data sets were analyzed qualitatively and quantitatively. The data were expressed by ratios and scores. Patients: Forty nonsedated patients (1 to 39 years, average age 2.7 years) with unilateral cleft lip, cleft lip and alveolus, or complete unilateral cleft in Cambodia. Results: The acquired 3D data sets (mean acquisition time: 2.5 seconds) from facial surfaces were of diagnostic quality in 27 of 40 patients (average age, 14.2 years). In these cases all anatomical structures could be mapped precisely by means of landmark positioning in the range of millimeters. A new method of systematic analysis could be elaborated, allowing for data set expression independent of size and growth factors. In children under age 3, the measuring procedure was of limited value because of motion artifacts and was successful in only 6% (1 of 15) of these patients. Conclusion: The system offers a solid and precise tool for 3D imaging of the complex cleft lip anatomy in compliant patients and is useful for preoperative cleft assessment and follow-up. However, the application is limited in moving infants or uncooperative adults because of scanning time and acquisition method. The development of motion tracking and faster devices could eliminate motion artifacts.
Skin toxicity of anti‐cancer therapy
2008-10-27

Summary Changes in skin and its adnexa such as hair follicles and nails are among the most common side effects of antineoplastic treatments. They pose a challenge with regard to diagnostic and therapeutic aspects. This article reviews the various cutaneous reactions to chemotherapy and their most common causative agents, the adverse events of radiation therapy, as well as the characteristic skin changes under treatment with new molecular‐driven targeted agents.
[Ph4P][(C5H6N3O3)M(CO)5] (M = Cr, Mo, W; C5H7N3O3 = 1,3‐Dimethyl‐cyanuric Acid). Organometallic Complexes of the 1,3‐Dimethylcyanurate Ligand
2008-10-27

Abstract 1,3‐Dimethylcyanuric acid (DMCH) forms on deprotonation and reaction with TlF its thallous salt Tl[DCM] ( 2 ) which is converted to the phosphonium salt [PPh 4 ][DCM] ( 3 ). On the reaction with M(CO) 6 , the pentacarbonylmetalate salts [Ph 4 P][(DMC)M(CO) 5 ], M = Cr ( 4a ), Mo ( 4b ) and W ( 4c ) are obtained. IR and NMR data of 4 reveal the DMC anion ( 1 ) to have coordination properties similar to those of pyridine. The crystal structures of 4a and 4c are reported.
Quantitative expression of the Candida albicans secreted aspartyl proteinase gene family in human oral and vaginal candidiasis
2008-10-28

A quantitative real-time RT-PCR system was established to identify which secreted aspartyl proteinase (SAP) genes are most highly expressed and potentially contribute to Candida albicans infection of human epithelium in vitro and in vivo. C. albicans SC5314 SAP1-10 gene expression was monitored in organotypic reconstituted human epithelium (RHE) models, monolayers of oral epithelial cells, and patients with oral (n=17) or vaginal (n=17) candidiasis. SAP gene expression was also analysed in Deltasap1-3, Deltasap4-6, Deltaefg1 and Deltaefg1/cph1 mutants to determine whether compensatory SAP gene regulation occurs in the absence of distinct proteinase gene subfamilies. In monolayers, RHE models and patient samples SAP9 was consistently the most highly expressed gene in wild-type cells. SAP5 was the only gene significantly upregulated as infection progressed in both RHE models and was also highly expressed in patient samples. Interestingly, the SAP4-6 subfamily was generally more highly expressed in oral monolayers than in RHE models. SAP1 and SAP2 expression was largely unchanged in all model systems, and SAP3, SAP7 and SAP8 were expressed at low levels throughout. In Deltasap1-3, expression was compensated for by increased expression of SAP5, and in Deltasap4-6, expression was compensated for by SAP2: both were observed only in the oral RHE. Both Deltasap1-3 and Deltasap4-6 mutants caused RHE tissue damage comparable to the wild-type. However, addition of pepstatin A reduced tissue damage, indicating a role for the Sap family as a whole in inducing epithelial damage. With the hypha-deficient mutants, RHE tissue damage was significantly reduced in both Deltaefg1/cph1 and Deltaefg1, but SAP5 expression was only dramatically reduced in Deltaefg1/cph1 despite the absence of hyphal growth in both mutants. This indicates that hypha formation is the predominant cause of tissue damage, and that SAP5 expression can be hypha-independent and is not solely controlled by the Efg1 pathway but also by the Cph1 pathway. This is believed to be the first study to fully quantify SAP gene expression levels during human mucosal infections; the results suggest that SAP5 and SAP9 are the most highly expressed proteinase genes in vivo. However, the overall contribution of the Sap1-3 and Sap4-6 subfamilies individually in inducing epithelial damage in the RHE models appears to be low.
Abstract 1964: Bone Morphogenetic Protein Antagonist “Protein Related to Dan and Cerberus” Promotes Differentiation of Embryonic Stem Cells to Atrial Cardiomyocytes
2008-10-28

The molecular factors that regulate cardiac differentiation have been extensively studied, yet, relatively little is known about how cardiomyocytes acquire atrial versus ventricular characteristics. Embryonic stem (ES) cells, which have the potential to differentiate to a wide array of distinct cell types, including most types of cardiovascular cells, offer a pertinent in vitro model to work out the molecular mechanisms of atrial specification and differentiation. We discovered that the secreted antagonist of BMP signaling, Protein Related to Dan and Cerberus (PRDC, also called Gremlin2) leads to a surge in cardiomyocytic differentiation when applied to mouse ES-derived cardiac progenitor cells. This property is unique to PRDC among tested BMP antagonists. Lineage expansion is restricted to cardiomyocytes, with the differentiation of endodermal, blood, endothelial and neuronal cells being unaffected. Using molecular and electrophysiological analyses, we show that PRDC-induced cardiomyocytes acquire atrial characteristics. Consistent with the in vitro results, we found that injection of PRDC mRNA into the developing zebrafish embryo leads to supernumerary contracting areas. The ectopic cardiomyocytes express atrial-, but not ventricular- specific cardiac genes. We determined that PRDC treatment induces the expression of COUP-TFII, a known transcriptional regulator of atrial differentiation, but suppresses Notch signaling. Inhibition of Notch is sufficient to induce atrial-specific genes; however, blocking Notch does not expand the cardiogenic fields. Taken together, our data suggest that antagonism of BMP and Notch signaling by PRDC is a critical early step in the specification, expansion and differentiation of atrial progenitor cells. This information might be relevant for treating atrial degeneration, as well as for understanding the etiology of atrial fibrillation.
Abstract 4374: G-CSF Treatment Improves Cardiac Function In postmyocarditic Cardiomyopathy By Enhanced Circulation And Homing Of CD34+ Progenitor Cell Populations
2008-10-28

Objective : Recently, it was shown that the physiologic repair mechanism of mobilization and homing of bone marrow-derived stem cells (BMCs) is impaired in dilated cardiomyopathy. In our study we aimed to analyze circulation and homing of CD34 + progenitor cell populations in a murine model of dilated cardiomyopathy due to coxsackie virus B3 (CVB3) induced myocarditis and the influence of G-CSF treatment on BMC homing and cardiac function. Methods and Results : First, SWR/J (H-2q)-mice were infected by intraperitoneal injection of 10 5 pfu CVB3. Healthy, age-matched SWR/J (H-2q)-mice served as controls. 12 weeks after infection, DCM was verified by MRI/Millar-tip-catheter and histology. In DCM mice, CD34 + BMC populations (CD34 + CD31 + , CD34 + Sca-1 + , CD34 + c-kit + and CD34 + CXCR-4 + ) measured by flow cytometry were significantly increased in peripheral blood, decreased in bone marrow and remained unchanged in the hearts in comparison to controls. Different from ischemic heart diseases, myocardial homing factors (SDF-1, SCF, HIF-1a, VCAM and HGF) assessed by real-time PCR were not upregulated in the CVB3-DCM group. Finally, 18 DCM-CVB3 mice were analyzed by MRI 8 weeks after CVB3 infection and randomized into G-CSF-or saline-treatment (100 μg/20μl s.c. daily for 2× 5 days). 12 weeks after infection, cardiac function was assessed using MRI: Change of ejection fraction was significantly better in the G-CSF-group compared to the controls (4.1±1.8 vs. −2.5±2.2%; p=0.03). The improvement of cardiac function was associated with enhanced homing of BMC subpopulations. Conclusions : We have shown that postmyocarditic cardiomyopathy is associated with a reduced migration of BMCs to the cardiomyopathic hearts due to a lack of increase of homing factors. This defect can partly be overcome by G-CSF-administration resulting in an increased number of stem cells in the myocardium and leading to a moderately improved cardiac function. Therefore our data provides new insights in the pathogenesis of dilated cariomyopathy and presents a promising non-invasive approach to ameliorate heart failure.
Glucagon Cell Adenomatosis: A Newly Recognized Disease of the Endocrine Pancreas
2008-10-29

The findings are sufficiently distinctive to suggest a new neoplastic disease of the endocrine pancreas that we recommend calling glucagon cell adenomatosis. Clinically, this disease may be an incidental finding, or it may lead to a glucagonoma syndrome.
Quantifying Cathepsin S Activity in Antigen Presenting Cells Using a Novel Specific Substrate
2008-10-29

Cathepsin S (CatS) is a lysosomal cysteine protease belonging to the papain superfamily. Because of the relatively broad substrate specificity of this family, a specific substrate for CatS is not yet known. Based on a detailed study of the CatS endopeptidase specificity, using six series of internally quenched fluorescent peptides, we were able to design a specific substrate for CatS. The peptide series was based on the sequence GRWHTVGLRWE-Lys(Dnp)-DArg-NH2, which shows only one single cleavage site between Gly and Leu and where every substrate position between P-3 and P-3' was substituted with up to 15 different amino acids. The endopeptidase specificity of CatS was mainly determined by the P-2, P-1', and the P-3' substrate positions. Based on this result, systematically modified substrates were synthesized. Two of these modified substrates, Mca-GRWPPMGLPWE-Lys(Dnp)-DArg-NH2 and Mca-GRWHPMGAPWE-Lys(Dnp)-DArg-NH2, did not react with the purified cysteine proteases cathepsin B (CatB) and cathepsin L (CatL). Using a specific CatS inhibitor, we could further show that these two peptides were not cleaved by endosomal fractions of antigen presenting cells (APCs), when CatS was inhibited and related cysteine proteases cathepsin B, H, L and X were still active. Although aspartic proteases like cathepsin E and cathepsin D were also present, our substrates were suitable to quantify cathepsin S activity specifically in APCs, including B cells, macrophages, and dendritic cells without the use of any protease inhibitor. We find that CatS activity differs significantly not only between the three types of professional APCs but also between endosomal and lysosomal compartments.
Antimicrobial host defense in the upper gastrointestinal tract
2008-10-29

Despite dominant expression of antimicrobial host peptides, oesophageal tissue shows a weakened potency to kill C. albicans. These data suggest an important role of yet unknown antimicrobial molecules.
Marching square
2008-10-29

This interactive learning object illustrates ambiguities of marching cubes. We depict them in 2D, that is, we regard squares instead of cubes. You may directly manipulate two circle objects. The objects are sampled on a regular grid (blue points) and the marching square algorithm approximates the objects with lines. Move the circles to adjacent locations to experience how we resolve ambiguities by an additional midpoint test.
Memory management for unification-based processing of typed feature structures
2008-10-29

We consider two alternatives for memory management in typed-feature-structure-based parsers by identifying structural properties of grammar signatures that may be of some predictive value in determining the consequences of those alternatives. We define these properties, summarize the results of a number of experiments on artificially constructed signatures with respect to the relative rank of their asymptotic cost at parse-time, and experimentally consider how they impact memory management.
Signal convolution
2008-10-29

This interactive teaching gem shows the convolution concept for continuous signals and discrete samples. Signals occurring frequently in computer graphics education are predefined; others can be drawn or integrated easily. We explain how the material can be used for in-class demonstration and for homework, and describe the experiences we made with two courses on image processing and introductionary computer graphics. Student reading is provided.
Pathomorphologic evaluation of pulmonary radiofrequency ablation
2008-10-30

Abstract BACKGROUND. Radiofrequency (RF) ablation is an increasingly applied technique. Promising results of hepatic RF ablation raised expectations of its capabilities for treatment of primary and secondary lung tumors. Because of different thermal and electrical properties of lung tissue, compared with liver tissue, a simple analogy of tissue response is not possible. The authors aimed to evaluate the effectiveness of image‐guided pulmonary RF ablation and to characterize pathomorphology of tissue response. METHODS. RF ablations of 11 pulmonary malignancies in 9 patients were performed under computed tomography (CT)‐guidance. Three days after RF ablation, surgical resection was performed followed by pathologic examination. Specimens were evaluated macroscopically, histologically by hematoxylin and eosin (H &amp; E) staining, terminal deoxy‐nucleotidyl transferase‐mediated nick end‐labeling (TUNEL), and electron microscopy. RESULTS. Tumor tissues and adjacent lung tissues were characterized by double‐strand fragmentation as determined by TUNEL. Ultrastructurally apoptotic bodies were found, indicating apoptotic cells. Criteria for tissue necrosis were not fulfilled by standard histological staining (H &amp; E), showing preserved tissue architecture and only few microscopic cellular details suggestive of tumor regression. Because of DNA fragmentation, as determined by TUNEL and results from electron microscopy, the authors confirmed the tumor tissue to be completely ablated in 10 (90.9%) cases. However, in 2 cases, a safety margin was absent. CONCLUSIONS. CT‐guided pulmonary RF ablation of pulmonary malignancies is a locally effective treatment. Three days after RF ablation, tumor tissue seemed to be thermally fixed still showing characteristics of vital tumor tissue in standard histological staining; however the tissue proved to be in regression toward coagulative necrosis verified ultrastructurally and by TUNEL. Cancer 2008. © 2008 American Cancer Society.
Hematopoietic cell–derived interferon controls viral replication and virus-induced disease
2008-10-30

Abstract Type I interferon (IFN-I) strongly inhibits viral replication and is a crucial factor in controlling virus infections and diseases. Cellular activation through pattern recognition receptors induces interferon production in a wide variety of hematopoietic and nonhematopoietic cell types, including dendritic cells, fibroblasts, hepatocytes, and cells of neuronal origin. The relative contribution of hematopoietic and nonhematopoietic cells to the overall interferon response is an important issue which has not been fully addressed. Using irf7−/− and wild-type bone marrow chimeras we analyzed the contribution of IFN-I from bone marrow–derived sources in the control of viral infections and immunopathology in mice. We found that during systemic cytopathic virus infection, hematopoietic cells were essential for production of IFN-I, inhibition of viral spread to peripheral organs, and limiting cell damage. In a model of autoimmune diabetes induced by noncytopathic virus infection, hematopoietic cell–derived IFN-I was essential for CD8+ T cell–dependent cytotoxicity in pancreatic β-islet cells and induction of diabetes. These data suggest that during systemic viral infection primarily hematopoietic cell–derived IFN-I controls viral replication and viral-induced disease.
Human muscle cells express the costimulatory molecule B7‐H3, which modulates muscle–immune interactions
2008-10-30

Abstract Objective Interactions between the family of B7 ligands and their receptors are increasingly recognized as crucial for stimulation and/or inhibition of immune responses. The present study was undertaken to examine the expression and functional relevance of B7 homolog 3 (B7‐H3), a novel B7 homolog attributed significant immunoregulatory functions, in human muscle cells in vivo and in vitro. Methods Thirty‐five muscle biopsy specimens obtained from patients with polymyositis, dermatomyositis, inclusion body myositis, or noninflammatory myopathies and normal controls were analyzed by immunohistochemistry for B7‐H3 expression. The expression of B7‐H3 protein on primary human myoblasts and TE671 muscle rhabdomyosarcoma cells was studied by flow cytometry and Western blot analysis. B7‐H3 small interfering RNA (siRNA) was used to study the impact of knockdown of B7‐H3 on CD8+ cell–mediated lysis in skeletal muscle cells. Results B7‐H3 was not detectable on normal muscle fibers. In contrast, its expression was markedly increased on muscle fibers from patients with inflammatory myopathies. Cell‐surface staining was most prominent in the contact areas between muscle fibers and inflammatory cells. B7‐H3 protein was detected on myoblasts cultured from control and myositis patient muscle tissue as well as in TE671 muscle rhabdomyosarcoma cells. Knockdown of B7‐H3 by siRNA in TE671 cells enhanced CD8+ T cell–specific lysis, indicating a functional role of B7‐H3 in the protection of skeletal muscle from immune‐mediated lysis. Conclusion Our results demonstrate that human muscle cells express B7‐H3, a functional coinhibitory molecule of the B7 family. B7‐H3 may play an important role in muscle–immune interactions, providing further evidence of the active role of muscle cells in local immunoregulatory processes.