julilili42/papers huggingface dataset:
Regulation of protein function by interfering protein species
2011-12-13

Abstract Most proteins do not function alone but act in protein complexes. For several transcriptional regulators, it is known that they have to homo- or heterodimerize prior to DNA binding. These protein interactions occur through defined protein-protein-interaction (PPI) domains. More than two decades ago, inhibitor of DNA binding (ID), a small protein containing a single helix-loop-helix (HLH) motif was identified. ID is able to interact with the larger DNA-binding basic helix-loop-helix (bHLH) transcription factors, but due to the lack of the basic domain required for DNA binding, ID traps bHLH proteins in non-functional complexes. Work in plants has, in the recent years, identified more small proteins acting in analogy to ID. A hallmark of these small negative acting proteins is the presence of a protein-interaction domain and the absence of other functional domains required for transcriptional activation or DNA binding. Because these proteins are often very small and function in analogy to microRNAs (meaning in a dominant-negative manner), we propose to refer to these protein species as ‘microProteins’ (miPs). miPs can be encoded in the genome as individual transcription units but can also be produced by alternative splicing. Other negatively acting proteins, consisting of more than one domain, have also been identified, and we propose to call these proteins ‘interfering proteins’ (iPs). The aim of this review is to state more precisely how to discriminate miPs from iPs. Therefore, we will highlight recent findings on both protein species and describe their mode of action. Furthermore, miPs have the ability to regulate proteins of diverse functions, emphasizing their value as biotechnological tools.
Hydration and interactions in protein solutions containing concentrated electrolytes studied by small-angle scattering
2011-12-14

During protein crystallization and purification, proteins are commonly found in concentrated salt solutions. The exact interplay of the hydration shell, the salt ions, and protein-protein interactions under these conditions is far from being understood on a fundamental level, despite the obvious practical relevance. We have studied a model globular protein (bovine serum albumin, BSA) in concentrated salt solutions by small-angle neutron scattering (SANS). The data are also compared to previous studies using SAXS. The SANS results for dilute protein solutions give an averaged volume of BSA of 91,700 Å(3), which is about 37% smaller than that determined by SAXS. The difference in volume corresponds to the contribution of a hydration shell with a hydration level of 0.30 g g(-1) protein. The forward intensity I(0) determined from Guinier analysis is used to determine the second virial coefficient, A(2), which describes the overall protein interactions in solution. It is found that A(2) follows the reverse order of the Hofmeister series, i.e. (NH(4))(2)SO(4) < Na(2)SO(4) < NaOAc < NaCl < NaNO(3) < NaSCN. The dimensionless second virial coefficient B(2), corrected for the particle volume and molecular weight, has been calculated using different approaches, and shows that B(2) with corrections for hydration and the non-spherical shape of the protein describes the interactions better than those determined from the bare protein. SANS data are further analyzed in the full q-range using liquid theoretical approaches, which gives results consistent with the A(2) analysis and the experimental structure factor.
Dynamics of highly concentrated protein solutions around the denaturing transition
2011-12-14

Using both quasi-elastic and fixed-window neutron spectroscopy, we study the dynamics of highly concentrated aqueous protein solutions of bovine serum albumin around the denaturing transition. For the temperature range 280 K &lt; T &lt; 370 K, the total mean-squared displacement 〈u 2〉 is recorded. Below and above the denaturing, we observe that 〈u 2〉 increases monotonically with T, but at the denaturing transition it decreases strongly. This observation can be rationalized and quantitatively modeled as a transition from a liquid protein solution to a gel-like state. Atomic vibrations, molecular subunit diffusion and, most importantly, diffusion of the entire protein determine 〈u 2〉. The latter is strongly hindered due to entanglement and cross-linking of the chains and causes the pronounced decrease of 〈u 2〉. Using information from the full quasi-elastic signal, we separate the diffusion contribution from 〈u 2〉 and reveal the transition temperature. For the analysis of this separation, we introduce a general concept, which is applicable to other colloid systems exhibiting both center-of-mass and internal dynamics.
Combined Muta‐ and Semisynthesis: A Powerful Synthetic Hybrid Approach to Access Target Specific Antitumor Agents Based on Ansamitocin P3
2011-12-14

Abstract Access of four new tumor specific folic acid/ansamitocin conjugates is reported that relies on a synthetic strategy based on the combination of mutasynthesis and semisynthesis. Two bromo‐ansamitocin derivatives were prepared by mutasynthesis or by a modified fermentation protocol, respectively, that served as starting point for the semisynthetic introduction of an allyl amine linker under Stille conditions. A sequence of standard coupling steps introduced the pteroic acid/glutamic acid/cysteine unit to the modified ansamitocins. All new derivatives, including those that are expected to be generated after internalization of the folic acid/ansamitocin conjugates into the cancer cell and reductive cleavage of the disulfide linkage showed good to strong antiproliferative activity (IC 50 &lt;10 n M ) for different cancer cell lines. Finally, the four conjugates were exposed to two cancer cell lines [cervix carcinoma, KB‐3‐1 (FR+) and lung carcinoma, A‐459 (FR−)], the latter devoid of the membrane‐bound folic acid receptor (FR−). All four conjugates showed strong antiproliferative activity for the FR+ cancer cell line but were inactive against the FR− cell line. The synthetic strategy pursued is based on the combination of mutasynthesis and semisynthesis and proved to be powerful for accessing new ansamitocin derivatives that are difficult to prepare by total synthesis.
The Open Graph Archive: A Community-Driven Effort
2011-12-14

A graphbase, a term coined by Knuth [7], is a database of graphs and computer programs that generate, analyze, manipulate, and visualize graphs. The terms graph library and graph archive are often used as synonyms for this term. Our vision is to provide an infrastructure and quality standards for a public graphbase, named the Open Graph Archive, that is accessible to researchers and other interested parties around the world via the worldwide web. This paper describes the current work undertaken towards this goal; the paper is also intended to be a call for participation since this will be a community-driven effort where most of the content will be provided by users of the system.
Mapping Aesthetic Musical Emotions in the Brain
2011-12-15

Music evokes complex emotions beyond pleasant/unpleasant or happy/sad dichotomies usually investigated in neuroscience. Here, we used functional neuroimaging with parametric analyses based on the intensity of felt emotions to explore a wider spectrum of affective responses reported during music listening. Positive emotions correlated with activation of left striatum and insula when high-arousing (Wonder, Joy) but right striatum and orbitofrontal cortex when low-arousing (Nostalgia, Tenderness). Irrespective of their positive/negative valence, high-arousal emotions (Tension, Power, and Joy) also correlated with activations in sensory and motor areas, whereas low-arousal categories (Peacefulness, Nostalgia, and Sadness) selectively engaged ventromedial prefrontal cortex and hippocampus. The right parahippocampal cortex activated in all but positive high-arousal conditions. Results also suggested some blends between activation patterns associated with different classes of emotions, particularly for feelings of Wonder or Transcendence. These data reveal a differentiated recruitment across emotions of networks involved in reward, memory, self-reflective, and sensorimotor processes, which may account for the unique richness of musical emotions.
Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX
2011-12-15

Suicidal death of erythrocytes, or eryptosis, is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Eryptosis is triggered by increase of cytosolic Ca 2+ activity, which may result from treatment with the Ca 2+ ionophore ionomycin or from energy depletion by removal of glucose. The present study tested the hypothesis that phosphatidylserine exposure at the erythrocyte surface fosters adherence to endothelial cells of the vascular wall under flow conditions at arterial shear rates and that binding of eryptotic cells to endothelial cells is mediated by the transmembrane CXC chemokine ligand 16 (CXCL16). To this end, human erythrocytes were exposed to energy depletion (for 48 h) or treated with the Ca 2+ ionophore ionomycin (1 μM for 30 min). Phosphatidylserine exposure was quantified utilizing annexin-V binding, cell volume was estimated from forward scatter in FACS analysis, and erythrocyte adhesion to human vascular endothelial cells (HUVEC) was determined in a flow chamber model. As a result, both, ionomycin and glucose depletion, triggered eryptosis and enhanced the percentage of erythrocytes adhering to HUVEC under flow conditions at arterial shear rates. The adhesion was significantly blunted in the presence of erythrocyte phosphatidylserine-coating annexin-V (5 μl/ml), of a neutralizing antibody against endothelial CXCL16 (4 μg/ml), and following silencing of endothelial CXCL16 with small interfering RNA. The present observations demonstrate that eryptotic erythrocytes adhere to endothelial cells of the vascular wall in part by interaction of phosphatidylserine exposed at the erythrocyte surface with endothelial CXCL16.
Intrinsic and Acquired Drug Resistance in Malignant Tumors
2011-12-15

Drug resistance is the major reason for failure in cancer chemotherapy. Resistance may be either pre-existent (intrinsic resistance), or induced by drugs (acquired resistance), So far, no strategy has been found to overcome resistance, which is based on highly complex and individually variable biological mechanisms. In present clinical practice, drug resistance can only be recognized during treatment, after long lag times. Thus diagnostic tests are re quired, indicating resistance at an earlier stage, in order to avoid unnecessary medication, frequently associated with toxic side-effects. A number of new anti-cancer drugs are now available. In contrast to the unspecifically acting cytostatic chemotherapy, these compounds have targeted actions. However, as recent studies have shown, resistances and severe side-effects can also be found with targeted drugs. With the increasing number of new treatment regimens, the early diagnosis of resistance will optimize therapy, and indeed will be indispensable for individual cancer therapy. The resistance assays available for use in clinical practice should be integrated into cancer therapy. Research into this neglected area needs to be intensified.
Charge-controlled metastable liquid–liquid phase separation in protein solutions as a universal pathway towards crystallization
2011-12-15

We demonstrate that a metastable liquid-liquid phase separation (LLPS) in protein aqueous solutions can be induced by multivalent metal ions at room temperature. We determine the salt and protein partitioning in the two coexisting phases. The structure factor obtained by small angle X-ray scattering provides direct evidence for a short-ranged attraction, which leads to the metastability of the LLPS. An extended phase diagram with three control parameters (temperature, protein and salt concentration) provides a conclusive physical picture consistent with a criterion for the second virial coefficient. The presented isothermal control mechanism of the phase behavior opens new perspectives for the understanding of controlled phase behavior in nature. Furthermore, we discuss the application of this framework in predicting and optimizing conditions for protein crystallization.
Circumstellar disks in binary star systems
2011-12-15

\\n Context. As of today, over 50 planetary systems have been discovered in binary star systems, some of which have binary separations that are smaller than 20 AU. In these systems the gravitational forces from the binary have a strong influence on the evolution of the protoplanetary disk and hence the planet formation process.\\n Aims. We study the evolution of viscous and radiative circumstellar disks under the influence of a companion star. We focus on the eccentric γ Cephei and α Centauri system as examples and compare disk quantities such as disk eccentricity and precession rate to previous isothermal simulations.\\n Methods. We performed two-dimensional hydrodynamical simulations of the binary star systems under the assumption of coplanarity of the disk, host star and binary companion. We used the grid-based, staggered mesh code FARGO with an additional energy equation to which we added radiative cooling based on opacity tables.\\n Results. The eccentric binary companion perturbs the disk around the primary star periodically. Upon passing periastron, spirals arms are induced that wind from the outer disk towards the star. In isothermal simulations this results in disk eccentricities up to edisk ≈ 0.2, but in more realistic radiative models we obtain much smaller eccentricities of about edisk ≈ 0.04−0.06 with no real precession. Models with varying viscosity and disk mass indicate that disks with less mass have lower temperatures and higher disk eccentricity. \\n Conclusions. The fairly high disk eccentricities, as indicated in previous isothermal disk simulations, implied a more difficult planet formation in the γ Cephei system caused by the enhanced collision velocities of planetesimals. We have shown that under more realistic conditions with radiative cooling the disk becomes less eccentric and thus planet formation may be made easier. However, we estimate that the viscosity in the disk has to very low, with α ≲ 0.001, because otherwise the disk’s lifetime will be too short to allow planet formation to occur along the core instability scenario. We estimate that the periodic heating of the disk in eccentric binaries will be observable in the mid-IR regime.\\n
The Mini-Cog versus the Mini-Mental State Examination and the Clock Drawing Test in daily clinical practice: screening value in a German Memory Clinic
2011-12-15

The Mini-Cog proved to have superior discriminatory power than either CDT or MMSE and is demonstrated to be a valid "short" screening instrument taking 3 to 4 minutes to administer in the geriatric setting.
The role of immunoglobulin A in prolonged and relapsing hepatitis A virus infections
2011-12-15

Hepatitis A virus (HAV) infections result in different courses of the disease, varying between normal, prolonged and relapsing. However, the reason for these heterogeneous clinical appearances is not understood. As HAV–anti-HAV IgA immunocomplexes (HAV–IgA) infect hepatocytes, IgA was postulated as a carrier supporting hepatotropic transport of HAV, and it was speculated that this carrier mechanism contributes to the various clinical outcomes. In this study, the IgA-carrier mechanism was investigated in a mouse model. We show that HAV–IgA immunocomplexes efficiently reached the liver not only in HAV-seronegative mice, but also, and this is in contrast to free-HAV particles, in immunized HAV-seropositive animals. This IgA-mediated transport of HAV to the liver in the presence of immunity depended on the stage of development of the immune response. We conclude that over a period of several weeks after infection, anti-HAV IgA is able to promote an enterohepatic cycling of HAV, resulting in continuous endogenous reinfections of the liver. Our experiments indicate that highly avid IgG antibodies, which are present at later times of the infection, can terminate the reinfections. However, the endogenous reinfections in the presence of a developing neutralizing immunity might contribute to prolonged as well as to relapsing courses of HAV infections. Furthermore, the results show that serum IgA may act as an infection protracting factor.
Multi-Resolution Sound Rendering
2011-12-15

Point-based multi-resolution representations have been used successfully for rendering highly complex three dimensional scenes in real-time. In this paper, we apply this paradigm to sound rendering: A hierarchy of stochastic sample sound sources is used to approximate complex sound environments (containing a large number of sound sources, such as a football stadium), allowing for interactive real-time walkthroughs. Additionally, the proposed technique can be used for observer-dependent auralizations of simple approximations of global sound propagation. Typical applications of the technique are in virtual reality and computer games, especially to complement established output-sensitive algorithms for rendering visual content.
Magnetic brain activity phase‐locked to the envelope, the syllable onsets, and the fundamental frequency of a perceived speech signal
2011-12-16

Abstract During speech perception, acoustic correlates of syllable structure and pitch periodicity are directly reflected in electrophysiological brain activity. Magnetoencephalography ( MEG ) recordings were made while 10 participants listened to natural or formant‐synthesized speech at moderately fast or ultrafast rate. Cross‐correlation analysis was applied to show brain activity time‐locked to the speech envelope, to an acoustic marker of syllable onsets, and to pitch periodicity. The envelope yielded a right‐lateralized M 100‐like response, syllable onsets gave rise to M 50/ M 100‐like fields with an additional anterior M 50 component, and pitch (ca. 100 Hz ) elicited a neural resonance bound to a central auditory source at a latency of 30 ms. The strength of these MEG components showed differential effects of syllable rate and natural versus synthetic speech. Presumingly, such phase‐locking mechanisms serve as neuronal triggers for the extraction of information‐bearing elements.
Assessment of dysplastic hematopoiesis: lessons from healthy bone marrow donors
2011-12-16

The poor reliability of the 10% cut off was partly related to the proximity of the current criteria to the observed cut-off mean values of the normal population. These findings question the current WHO threshold of the 10% or over necessary for the percentage of cells manifesting dysplasia to be considered significant, and suggest that either a higher threshold would be more appropriate or different thresholds should be set for each lineage.
The neural correlates of impaired collision avoidance in hemianopic patients
2011-12-16

Abstract. Purpose: The aim of this study was to assess the brain regions associated with impaired performance in a virtual, dynamic collision avoidance task, in a group of patients with homonymous visual field defects (HVFDs) because of unilateral vascular brain lesions. Methods: Overall task performance was quantitatively assessed as the number of collisions while crossing an intersection at two levels of traffic density. Twenty‐six patients were divided into two subgroups using the median split method: patients with ‘performance above average’ (HVFD A , i.e. lower number of collisions) and patients with ‘performance below average’ (HVFD B , i.e. higher number of collisions). In order to identify the anatomical structures that might be specifically affected in HVFD B patients but spared in HVFD A patients, overlap, subtraction and voxel‐based lesion‐symptom mapping analyses were performed using the MRIcron software. Results: No significant difference in collision avoidance between patients with left‐ and right‐hemispheric lesions was revealed. Separate lesion analysis in 12 patients with right‐ and 14 patients with left‐hemispheric lesions showed that the cortical structures associated with impaired collision avoidance were the parieto‐occipital region and posterior cingulate gyrus in the right hemisphere and the inferior occipital cortex and parts of the fusiform (occipito‐temporal) gyrus in the left hemisphere. Conclusion: In the present collision avoidance paradigm, impaired performance of patients with right ‐hemispheric lesions is associated with damage in the dorsal processing stream and potential impact on the visual spatial working memory (WM), while impaired performance of patients with left ‐hemispheric lesions is associated with damage in the ventral stream and potential impact on the visual object WM.
Prevalence of Dihydrofolate Reductase Gene Mutations in Plasmodium falciparum Isolate from Pregnant Women in Nigeria
2011-12-16

We assessed the prevalence of Plasmodium falciparum and the frequency of the dhfr triple mutation that is associated with antifolate drug resistance among P. falciparumisolates obtained from pregnant women in Ilorin, Nigeria. The study included 179 women in the second and third trimester of pregnancy who have been exposed to intermittent preventive treatment in pregnancy (IPTp) with sulfadoxinepyrimethamine. Thick and thin blood films and PCR were used for malaria parasite detection. Blood group and hemoglobin concentration were also determined. Mutations in P. falciparum dhfr were analyzed by sequencing DNA obtained from blood spots on filter paper. Prevalence of P. falciparum in the population (PCR corrected) was 44.1% (79/179) with 66.7% and 33.3% in the second and third trimester, respectively. Primigravide (51.3%) were more infected than multigravide (48.7%) but the difference was not statistically significant. Women in blood group A had the highest P. falciparum malaria infection (30.8%). The mean hemoglobin concentration was lower among those infected with malaria parasite. Also, more women with the malaria parasite (38.4%) had anemia compare to those without (21.4%). The prevalence of the P. falciparum dhfr mutant alleles was 64.1%, 61.5%, 38.5%, and 12.8% for I51, R59, N108 and T108, respectively. None of the samples had the L164 mutation. The combined triple dhfr mutation (51 + 59 + 108) in the population was 17.9% (7 of 39). Also, the prevalence of the triple mutant alleles was not significantly associated to the number of doses of SP taken by the women. These findings highlight the need for a regular assessment of IPTp/SP efficacy, and evaluation of possible alternative drugs.