julilili42/papers huggingface dataset:
Assembly of mRNA-Protein Complexes for Directional mRNA Transport in Eukaryotes - An Overview
2012-07-01

At all steps from transcription to translation, RNA-binding proteins play important roles in determining mRNA function. Initially it was believed that for the vast majority of transcripts the role of RNA-binding proteins is limited to general functions such as splicing and translation. However, work from recent years showed that members of this class of proteins also recognize several mRNAs via cis-acting elements for their incorporation into large motor-containing particles. These particles are transported to distant subcellular sites, where they become subsequently translated. This process, called mRNA localization, occurs along microtubules or actin filaments, and involves kinesins, dyneins, as well as myosins. Although mRNA localization has been detected in a large number of organisms from fungi to humans, the underlying molecular machineries are not well understood. In this review we will outline general principles of mRNA localization and highlight three examples, for which a comparably large body of information is available. The first example is She2p/She3p-dependent localization of ASH1 mRNA in budding yeast. It is particularly well suited to highlight the interdependence between different steps of mRNA localization. The second example is Staufen-dependent localization of oskar mRNA in the Drosophila embryo, for which the importance of nuclear events for cytoplasmic localization and translational control has been clearly demonstrated. The third example summarizes Egalitarian/Bicaudal D-dependent mRNA transport events in the oocyte and embryo of Drosophila. We will highlight general themes and differences, point to similarities in other model systems, and raise open questions that might be answered in the coming years.
The wolf in sheep’s clothing
2012-07-01

Metastasis is strongly inhibited in thrombocytopenic mice. This phenotype is reversed by NK cell depletion which indicates that platelets may facilitate tumor progression and metastasis by interfering with NK cell immunosurveillance. Understanding the underlying mechanisms may help us to reinforce anti-tumor immunity and NK-based immunotherapy in cancer patients.
Platelets in Atherothrombosis - Diagnostic and Prognostic Value of Platelet Activation in Patients with Atherosclerotic Diseases
2012-07-01

Platelets and their activation have a pivotal role in the development of atherosclerotic diseases such as acute myocardial infarction (AMI), stroke and peripheral arterial occlusion. Biomarkers of platelet activation are making inroads into clinical studies and may serve as promising agents upstream to established downstream markers of myocardial necrosis such as troponin and creatin kinase. Targeting the degree of platelet activation assessed by the key collagen receptor of platelet activation, glycoprotein VI (GPVI), may have diagnostic and prognostic value for the assessement of high-risk groups of patients with symptomatic coronary artery disease and ischemic stroke and may be worthwhile to help to facilitate clinical decision-making and to rapidly initiate adequate therapy. The concert of platelet count, platelet activation, platelet aggregation and subsequent inflammation has had a significant impact on the clinical outcome in patients with atherosclerotic diseases. For a therapeutical approach to ameliorate prognosis, the use of antiplatelet treatment in particular in AMI patients with low response to clopidogrel has partly been overcome by novel second antiplatelet drugs on top of aspirin such as prasugrel and ticagrelor. Antiplatelet therapy may be adapted according to a GPVI-based platelet activity monitoring along with aggregometry of residual platelet aggregation. Other approaches using protease-activated receptor- 1 antagonists vorapaxar or atopaxar, which inhibit the platelet thrombin receptor, soluble GPVI called Revacept©, which blocks the collagen binding sites at the vascular lesion and anopheline saliva protein derived from the malaria vector mosquito, a platelet adhesion inhibitor independent of a GPVI mechanism, still wait for their breakthrough.
One pot radiofluorination of a new potential PSMA ligand [Al18F]NOTA‐DUPA‐Pep
2012-07-01

Up to now, many radiolabeled ligands targeting prostate‐specific membrane antigen (PSMA) have been synthesized. To carry out radiofluorinations, there have been several approaches mainly involving two steps of radiosynthesis. However, in case of labelings with high activities, one radiosynthetic step (‘one pot synthesis’) is highly desirable. As an alternative, radiofluorinations of peptides coupled to the NOTA complex via Al 18 F appear to be very promising, both in terms of feasible labelling procedure and stability in vivo . Therefore, in the present study, we synthesized a new PSMA‐ligand, that is, NOTA‐DUPA‐Pep, labeled with Al 18 F and examined the reaction kinetics in dependence on temperature, time, concentration of precursor, and AlCl 3 solution. Highest radiochemical yields of 83 ± 1.1% were obtained at 105 °C after 15 min of reaction time. At the end of synthesis, [Al 18 F]NOTA‐DUPA‐Pep was prepared with a radiochemical purity of ≥98% with an overall yield of 79 ± 0.7% ( n = 3) (decay uncorrected) within 55 min. Copyright © 2012 John Wiley &amp; Sons, Ltd.
FIRES and NORSE are distinct entities
2012-07-01

To the Editors: Recently, a brief communication was published in Epilepsia (Ismail & Kossoff, 2011) concerning new-onset refractory status epilepticus (NORSE) and fever-induced refractory epileptic encephalopathy syndrome (FIRES). The authors of this article proposed that these syndromes are the same entities. In our view, these syndromes are distinct diseases with different underlying pathomechanisms. Certainly, a small population described by Glaser et al. (2008) in the California Encephalitis Project might present with overlapping features, such as devastating outcome, rare pathologic alterations on cerebral magnetic resonance imaging (cMRI), and only mild changes in the cerebrospinal fluid. However, FIRES appears in children 2–17 years of age (mainly between the age 4 and 9), and is characterized by a fever-induced refractory status epilepticus (rSE) (van Baalen et al., 2010). In contrast, NORSE has often been described as rSE in adulthood (18–53 years), but not always with preceding febrile illness. Furthermore, NORSE shows a clear preponderance (4:1) in women (at ages 20–32 years) (e.g., Costello et al., 2009 and our own unpublished data), whereas slightly more men (57%) are affected in FIRES (Kramer et al., 2011). Electroencephalography results in patients with FIRES show focal epileptic activity with predominance in the temporal or frontal lobe (Kramer et al., 2011), whereas in NORSE, multifocal activity has been reported without a focal preponderance, indicating a more unspecific origin (Costello et al., 2009). In both entities, the underlying cause is enigmatic. We propose that considering the young age of onset, a genetic coetiology might be worth pursuing in FIRES; in NORSE, such a genetic etiology is not very likely. Because these disorders appear to affect two distinct populations and present with different clinical symptoms, we believe that they should not be mixed up. The authors have no conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
T2 and DWI in Pilocytic and Pilomyxoid Astrocytoma with Pathologic Correlation
2012-07-01

Objective: To quantify and compare T2 signal and apparent diffusion coefficient (ADC) in pilocytic and pilomyxoid astrocytoma (PA and PMA) and correlate results with myxoid content. Methods: Echo-planar diffusion weighted images (DWI) and standard magnetic resonance imaging (MRI) findings were reviewed retrospectively in patients with PA (n=34) and PMA (n=8). Regions of interest (ROIs) were drawn on ADC maps within tumor parts with lowest ADC values. Apparent diffusion coefficient values in tumor were normalized to those in cerebrospinal fluid (ADC/CSF). The ratio of T2 signal intensity in solid tumor parts to CSF (T2/CSF) was registered. Myxoid matrix was histologically quantified retrospectively in 8 PMAs and 17 PAs and correlated with imaging findings. Results: Mean ADC/CSF for PA and PMA was 0.53±0.10 and 0.69±0.10 (p&lt;0.01). Mean T2/CSF for PA and PMA was 0.78±0.19 and 0.93±0.09 (p&lt;0.01). Mean proportion of myxoid tumor matrix in PA was 50% (range, 10-100%) and 93% (range, 90-100%) in PMA (p=0.004). Eight patients (32%; all PA) had less than 50% myxoid content and 17 (68%; 8 PA; 9 PMA) had more. There was positive correlation of ADC/CSF, T2/CSF and ADC (r 2 =0.61, 0.65 and 0.60 respectively) and significant difference between the groups with more and less than 50% myxoid content (p=0.01 for ADC/CSF and T2/CSF and p=0.02 for ADC). Conclusions: General imaging features of PA and PMA are non-specific, ADC values and T2 signal intensity are generally higher in the latter, reflecting the proportion of myxoid matrix in these tumors.
An Experimental Study of a Flux Modulated Solid State Metathesis Reaction
2012-07-01

Abstract A solid state metathesis (SSM) reaction was investigated with respect to the formation of rare‐earth carbodiimides, the role of the co‐produced salt (LiCl), and the eutectic flux medium (LiCl/KCl). A SSM reaction is characterized by an exothermic reaction in which a salt (often LiCl) is coproduced. When the salt melts, it can serve as a useful medium for the crystallization of a desired product. An improved crystal growth can be observed by using an eutectic flux. However, the composition of an eutectic LiCl/KCl flux is altered when LiCl is produced during the reaction. The thermal effects concerning the endothermic melting of the flux and the exothermic ingnition of the SSM reaction may compensate each other, which is not necessarily a drawback for the reaction to proceed.
Platelet Activation in Alzheimer’s Disease: From Pathophysiology to Clinical Value
2012-07-01

Vascular risk factors and atherosclerosis are critically involved in dementia development of both vascular and Alzheimer's type. However, the exact mechanisms linking atherosclerosis and the development of Alzheimer's disease (AD) are still unknown. As platelet activation and adhesion on vascular wall is the first step of vascular inflammation and atherosclerosis, it appears tempting to hypothesize that platelets could be the link between vascular risk factors/ atherosclerosis and AD. In recent years, much work has been accomplished to elucidate the role of platelets in AD. The present review will summarize and highlight the latest findings of this research area and provide novel insight and understanding in the association between platelet activation and AD.
Role of Ion Transport in Control of Apoptotic Cell Death
2012-07-01

Abstract Cell shrinkage is a hallmark and contributes to signaling of apoptosis. Apoptotic cell shrinkage requires ion transport across the cell membrane involving K + channels, Cl − or anion channels, Na + /H + exchange, Na + ,K + ,Cl − cotransport, and Na + /K + ATPase. Activation of K + channels fosters K + exit with decrease of cytosolic K + concentration, activation of anion channels triggers exit of Cl − , organic osmolytes, and HCO 3 − . Cellular loss of K + and organic osmolytes as well as cytosolic acidification favor apoptosis. Ca 2+ entry through Ca 2+ ‐permeable cation channels may result in apoptosis by affecting mitochondrial integrity, stimulating proteinases, inducing cell shrinkage due to activation of Ca 2+ ‐sensitive K + channels, and triggering cell‐membrane scrambling. Signaling involved in the modification of cell‐volume regulatory ion transport during apoptosis include mitogen‐activated kinases p38, JNK, ERK1/2, MEKK1, MKK4, the small G proteins Cdc42, and/or Rac and the transcription factor p53. Osmosensing involves integrin receptors, focal adhesion kinases, and tyrosine kinase receptors. Hyperosmotic shock leads to vesicular acidification followed by activation of acid sphingomyelinase, ceramide formation, release of reactive oxygen species, activation of the tyrosine kinase Yes with subsequent stimulation of CD95 trafficking to the cell membrane. Apoptosis is counteracted by mechanisms involved in regulatory volume increase (RVI), by organic osmolytes, by focal adhesion kinase, and by heat‐shock proteins. Clearly, our knowledge on the interplay between cell‐volume regulatory mechanisms and suicidal cell death is still far from complete and substantial additional experimental effort is needed to elucidate the role of cell‐volume regulatory mechanisms in suicidal cell death. © 2012 American Physiological Society. Compr Physiol 2:2037‐2061, 2012.
When does goal discrepancy induce compensatory effort? An application of self‐completion theory to social issues
2012-07-01

Abstract The authors review research that applies self‐completion theory to goals targeting other people (as in the case of stereotyping and prejudice), goals that aim at the achievement of a certain social identity and goals based on the social identity. It is demonstrated that goal discrepancies lead to compensation for social as well as for non‐social goals. Based on self‐completion theory it is proposed that the identity‐relevance of the respective goal as well as the goal relevance of the subsequent task are of major importance considering the individuals’ compensation. The authors argue that the consideration of these factors advance our understanding of social phenomena.
Surgical Treatment of a Young Patient with Bilaterally Destroyed First Metatarsophalangeal Joints Suffering from Gout
2012-07-01

The authors present an unusual case of untreated gout leading to major bony destructions in both metatarsophalangeal joints, leading to joints of enormous dimensions. If untreated, gout can cause disabling destructions with direct influence on both private and working life, even in young patients. In potentially noncompliant patients, simple surgical procedures and postoperative regimes are valuable treatment options resulting in acceptable clinical results. (J Am Podiatr Med Assoc 102(4): 334–337, 2012)
Time‐dependent column performance of cholesterol‐based stationary phases for HPLC by LC characterization and solid‐state NMR spectroscopy
2012-07-01

Three different cholesterol‐based stationary phases were investigated with respect to their time‐dependent separation behavior. The examined stationary phases differ in the used spacer molecule and the synthesis route and were used under routine laboratory conditions over a period of two years. The chromatographic behavior of the three phases was determined by using a standard reference material in addition to a separation of a steroid mixture. The surface chemistry and the modification of these with the chemically bonded moiety were investigated with nuclear magnetic resonance ( NMR) spectroscopy and elemental analysis. Through applying different techniques we determined changes in retention and selectivity; solid‐state NMR spectra showed changes in the surface chemistry dependent on the synthesis route. Superior long‐term stability was observed for the undecanoate‐cholesterol ( UDC‐C hol) column in terms of hydrophobic retentiveness and selectivity.
Therapeutic Potential and Strategies Against Leukocyte-Platelet Interaction in Atherosclerosis
2012-07-01

Leukocyte rolling, adhesion, transmigration and activation are features of vascular inflammation leading to atherosclerosis. In particular the interaction between platelets and leukocytes is a key process for adhesion of inflammatory cells to the vascular wall. The various mechanisms of the specific platelet-leukocyte interaction may provide a powerful target to prevent initiation and/or progression of atherosclerotic lesions.
P3‐177: Combining classical conditioning and brain‐state classification for the development of a brain‐computer interface (BCI) for Alzheimer's patients
2012-07-01

Alzheimer's Disease (AD) patients who have lost the ability to communicate verbally may benefit from a Brain-Computer Interface (BCI), which could allow them to convey basic thoughts and emotions, e.g. by associating affirmative and non-affirmative thinking to a positive and a negative emotion, respectively. One possibility to develop a BCI that can be used with AD patients is to modulate brain responses with a semantic classical conditioning paradigm, in order to associate congruent and incongruent word pairs with emotionally positive and negative stimuli, facilitating the discrimination between "affirmative" and "non-affirmative" thinking. Using a classical conditioning paradigm is convenient, since it does not require AD patients to put active effort in learning how the BCI works. In our classical conditioning paradigm, already tested on 11 healthy subjects, the unconditioned stimuli consist of a positive and negative emotional sound (a baby laugh and a scream, respectively). The conditioned stimuli, presented aurally, are congruent (e.g. 'fruit-apple') and incongruent (e.g. 'fruit-dog') word pairs. During the conditioning acquisition, congruent and incongruent word pairs are associated to the baby laugh and the scream respectively. Functional magnetic resonance imaging (fMRI) will be performed on AD patients (Mini Mental State Examination score: 18–24; intact auditory system) on a 3T scanner. To classify the signals corresponding to congruent and incongruent word pairs, both univariate (General Linear Model) and multivariate (Support Vector Machine, SVM) analyses will be performed. Both univariate and multivatiate analyses on healthy subjects confirmed the possibility to discriminate between affirmative and non-affirmative responses. We hypothesize that a similar differentiation may be found in AD patients, since classical conditioning was demonstrated to be possible, at least to some extent, in these patients.The study with AD patients is ongoing, and preliminary results will be presented during the conference. The encouraging results obtained with healthy subjects show that basic affirmative/non affirmative thinking discrimination is possible within an fMRI-BCI setting. The development of a BCI for AD patients could be an important step for allowing not only basic communication, but possibly lending a path for rehabilitation and diagnosis.
Platelets in Cardiovascular Imaging
2012-07-01

Coronary artery disease remains a major hazard within the western world despite early revascularisation and advanced medical therapy strategies. One of its major substrates is platelet activation and thrombus formation, triggering acute events such as myocardial infarction and ischemic strokes. There are a variety of non-invasive imaging strategies being translated from bench to bedside into clinical practice that tackle specific aspects of the pathophysiology of thrombus formation. Some of those techniques are able to visualize native contrast differences between thrombus and surrounding tissue, others focus on the use of specific contrast agents targeting thrombotic components such as fibrin or activated platelets. Some of those techniques are still in the pre-clinical stage; others have already entered the clinical arena. The current review article will introduce different techniques and their stage of development on their way from bench to bedside with a specific focus on cardiac magnetic resonance imaging, that has evolved over the last years providing high quality information on anatomy, perfusion and myocardial tissue characteristics such as scarring in clinical practice. Finally, we will give an outlook on how this exciting field might evolve in the future.
Influence of PAC properties on membrane performance in a PAC-UF hybrid system
2012-07-01

The combination of ultrafiltration (UF) and powdered activated carbon (PAC) has gained in importance over the last 15 years. The aim of applying PAC-UF hybrid processes is to improve the rejection capacity and the performance of membrane processes. In this work the influence of PAC-addition on membrane flux decline and fouling formation was studied with a submerged module using different water matrices. The PACs used were characterized by measurements of the surface area, the particle size distribution and the surface charge to get a better understanding of the observed effects. Results showed that the membrane flux decline was dependent on the applied type of activated carbon. When adding Picachem 8P, the transmembrane pressure (TMP) increased very quickly and the membrane performance was even worse than that without PAC. However, when adding Norit SA-UF under identical filtration conditions, the TMP was stable and the membrane performance was better than that without PAC. The fouling layers of the two PACs applied showed entirely different structures. Therefore the selection of a suitable PAC is a main factor for the overall performance of PAC-UF hybrid systems with submerged membranes.
Heterocycles [c]-Fused onto Indoloquinoxaline. Synthesis of Novel Pyrano[2’,3’:4,5]indolo[2,3-b]quinoxalin-2-ones
2012-07-01

A synthesis of 4-methylpyrano[2,3-e]indole-2,8,9-trione (5) is achieved from 7-amino-4- methylcoumarin by adopting the classical Sandmeyer methodology. The cyclocondensation reaction of pyrano-isatin 5 with the appropriately substituted o-phenylenediamines 6 in polyphosphoric acid proceeded regioselectively to furnish the respective pyrano[2’,3’:4,5]indolo[2,3-b]quinoxalines 7a - c. Structural assignments of the new compounds are based on microanalytical and spectral (IR, MS and NMR) data.
Novel Antiplatelet Therapy in Acute Coronary Syndromes: What is New in the Pipeline?
2012-07-01

Acute coronary syndromes (ACS) are triggered by enhanced platelet activation and aggregation. Hence, a cornerstone of successful secondary prevention in ACS is an effective platelet inhibition. Additionally, coronary interventions (PCI) lead to even increased artherothrombotic risks, another challenge in preventing recurrent events including stent thrombosis. Promising platelet targets were characterized and novel molecules were developed that are currently under investigation. Intensified antiplatelet therapy includes the risk of major bleeding which itself increases the mortality rate. Previous strategies of antiplatelet therapy were based on an "one-size fits all" concept. However, there has been evidence that variability of drug response exists and represents a clinically relevant issue. This observation is in line with results of randomized clinical trials that standard-of-care antiplatelet therapy is not sufficient to reduce cardiovascular (CV) risk in certain subgroups of ACS patients. In the last years, novel antiplatelet substances have entered the clinical arena and others are currently under investigation in phase II and III clinical trials. These include 3rd generation thienopyridine (prasugrel, elinogrel), ATP analogs (Ticagrelor, cangrelor), and non-ADP-receptor blocking antiplatelet substances like thrombin receptor antagonists. These agents have shown promising results in pilot studies and recent randomized trials. As the prevention of atherothrombotic risk is at the expense of bleeding risk, it will be a future task to clearly define patients' groups and subsets of ACS for the best net clinical benefit. This article focuses on the role of novel antiplatelet substances to reduce CV risk in ACS, discuss clinical implications and their potential future role.