Central potentials for polyatomic molecules. 1 - A survey of morse potentials determined from viscosity and the second virial coefficient

Morse potential function used to approximate pair interaction potential for wide variety of hydrocarbons determined from viscosity and second virial coefficien

Nucleoli and Promyelocytic Leukemia Protein (PML) bodies are phase separated nuclear protein quality control compartments for misfolded proteins

We uncovered a role for nucleoli and PML-bodies as phase-separated protein quality control organelles that compartmentalize protein quality control factors and misfolded proteins for their efficient clearance. Failure to dispose misfolded proteins converts nucleoli and PML-bodies into a solid state that immobilizes ubiquitin, limiting its recycling for genome integrity maintenance

A context-based approach for partitioning big data

In recent years, the amount of available data keeps growing at fast rate, and it is therefore crucial to be able to process them in an efficient way. The level of parallelism in tools such as Hadoop or Spark is determined, among other things, by the partitioning applied to the dataset. A common method is to split the data into chunks considering the number of bytes. While this approach may work well for text-based batch processing, there are a number of cases where the dataset contains structured information, such as the time or the spatial coordinates, and one may be interested in exploiting such a structure to improve the partitioning. This could have an impact on the processing time and increase the overall resource usage efficiency. This paper explores an approach based on the notion of context, such as temporal or spatial information, for partitioning the data. We design a context-based multi-dimensional partitioning technique that divides an n 12dimensional space into splits by considering the distribution of the each contextual dimension in the dataset. We tested our approach on a dataset from a touristic scenario, and our experiments show that we are able to improve the efficiency of the resource usage

What is the role of context in fair group recommendations?

We investigate the role played by the context, i.e. the situation the group is currently experiencing, in the design of a system that recommends sequences of activities as a multi-objective optimization problem, where the satisfaction of the group and the available time interval are two of the functions to be optimized. In particular, we highlight that the dynamic evolution of the group can be the key contextual feature that has to be considered to produce fair suggestions

BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity.

A homozygous disruption or genetic mutation of the bag3 gene causes progressive myofibrillar myopathy in mouse and human skeletal and cardiac muscle disorder while mutations in the small heat shock protein αB-crystallin gene (CRYAB) are reported to be responsible for myofibrillar myopathy. Here, we demonstrate that BAG3 directly binds to wild-type αB-crystallin and the αB-crystallin mutant R120G, via the intermediate domain of BAG3. Peptides that inhibit this interaction in an in vitro binding assay indicate that two conserved Ile-Pro-Val regions of BAG3 are involved in the interaction with αB-crystallin, which is similar to results showing BAG3 binding to HspB8 and HspB6. BAG3 overexpression increased αB-crystallin R120G solubility and inhibited its intracellular aggregation in HEK293 cells. BAG3 suppressed cell death induced by αB-crystallin R120G overexpression in differentiating C2C12 mouse myoblast cells. Our findings indicate a novel function for BAG3 in inhibiting protein aggregation caused by the genetic mutation of CRYAB responsible for human myofibrillar myopathy

Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site

<p>Abstract</p> <p>Background</p> <p>Ricin is a potent toxin and known bioterrorism threat with no available antidote. The ricin A-chain (RTA) acts enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship between ligand binding and RTA active site conformational change, we used a fragment-based approach to find a minimal set of bonding interactions able to induce rearrangements in critical side-chain positions.</p> <p>Results</p> <p>We found that the smallest ligand stabilizing an open conformer of the RTA active site pocket was an amide group, bound weakly by only a few hydrogen bonds to the protein. Complexes with small amide-containing molecules also revealed a switch in geometry from a parallel towards a splayed arrangement of an arginine-tryptophan cation-pi interaction that was associated with an increase and red-shift in tryptophan fluorescence upon ligand binding. Using the observed fluorescence signal, we determined the thermodynamic changes of adenine binding to the RTA active site, as well as the site-specific binding of urea. Urea binding had a favorable enthalpy change and unfavorable entropy change, with a ΔH of -13 ± 2 kJ/mol and a ΔS of -0.04 ± 0.01 kJ/(K*mol). The side-chain position of residue Tyr80 in a complex with adenine was found not to involve as large an overlap of rings with the purine as previously considered, suggesting a smaller role for aromatic stacking at the RTA active site.</p> <p>Conclusion</p> <p>We found that amide ligands can bind weakly but specifically to the ricin active site, producing significant shifts in positions of the critical active site residues Arg180 and Tyr80. These results indicate that fragment-based drug discovery methods are capable of identifying minimal bonding determinants of active-site side-chain rearrangements and the mechanistic origins of spectroscopic shifts. Our results suggest that tryptophan fluorescence provides a sensitive probe for the geometric relationship of arginine-tryptophan pairs, which often have significant roles in protein function. Using the unusual characteristics of the RTA system, we measured the still controversial thermodynamic changes of site-specific urea binding to a protein, results that are relevant to understanding the physical mechanisms of protein denaturation.</p

What makes spatial data big? A discussion on how to partition spatial data

The amount of available spatial data has significantly increased in the last years so that traditional analysis tools have become inappropriate to effectively manage them. Therefore, many attempts have been made in order to define extensions of existing MapReduce tools, such as Hadoop or Spark, with spatial capabilities in terms of data types and algorithms. Such extensions are mainly based on the partitioning techniques implemented for textual data where the dimension is given in terms of the number of occupied bytes. However, spatial data are characterized by other features which describe their dimension, such as the number of vertices or the MBR size of geometries, which greatly affect the performance of operations, like the spatial join, during data analysis. The result is that the use of traditional partitioning techniques prevents to completely exploit the benefit of the parallel execution provided by a MapReduce environment. This paper extensively analyses the problem considering the spatial join operation as use case, performing both a theoretical and an experimental analysis for it. Moreover, it provides a solution based on a different partitioning technique, which splits complex or extensive geometries. Finally, we validate the proposed solution by means of some experiments on synthetic and real datasets

Association entre la dégénérescence maculaire liée à l’âge et les parodontites

Purpose: To evaluate the association between age-related macular degeneration (AMD) and periodontal disease, two frequent conditions in the elderly, with some risk factors in common. Methods: Single center, pilot, case-control study performed in a center specialized in the diagnosis and management of AMD. Periodontal status was evaluated in 43 AMD patients and 19 controls. Fundus examination and a complete periodontal examination were performed in all subjects. Results: AMD patients have a greater percentage of 3–4 mm clinical attachment loss compared to controls (47% vs. 38%, [P = 0.039]). However, no significant difference was found between the groups with regard to the prevalence of severe periodontitis. Conclusions: These results suggest an association between AMD and attachment loss characteristic of periodontal disease and support the need for larger prospective studies to elucidate the relationships between these 2 highly prevalent and potentially severe diseases

ADAP2 in heart development: a candidate gene for the occurrence of cardiovascular malformations in NF1 microdeletion syndrome

Background Cardiovascular malformations have a higher incidence in patients with NF1 microdeletion syndrome compared to NF1 patients with intragenic mutation, presumably owing to haploinsufficiency of one or more genes included in the deletion interval and involved in heart development. In order to identify which genes could be responsible for cardiovascular malformations in the deleted patients, we carried out expression studies in mouse embryos and functional studies in zebrafish. Methods and results The expression analysis of three candidate genes included in the NF1 deletion interval, ADAP2, SUZ12 and UTP6, performed by in situ hybridisation, showed the expression of ADAP2 murine ortholog in heart during fundamental phases of cardiac morphogenesis. In order to investigate the role of ADAP2 in cardiac development, we performed loss-of-function experiments of zebrafish ADAP2 ortholog, adap2, by injecting two different morpholino oligos (adap2-MO and UTR-adap2-MO). adap2-MOs-injected embryos (morphants) displayed in vivo circulatory and heart shape defects. The molecular characterisation of morphants with cardiac specific markers showed that the injection of adap2-MOs causes defects in heart jogging and looping. Additionally, morphological and molecular analysis of adap2 morphants demonstrated that the loss of adap2 function leads to defective valvulogenesis, suggesting a correlation between ADAP2 haploinsufficiency and the occurrence of valve defects in NF1-microdeleted patients. Conclusions Overall, our findings indicate that ADAP2 has a role in heart development, and might be a reliable candidate gene for the occurrence of cardiovascular malformations in patients with NF1 microdeletion and, more generally, for the occurrence of a subset of congenital heart defects

Defective ribosomal products challenge nuclear function by impairing nuclear condensate dynamics and immobilizing ubiquitin

Nuclear protein aggregation has been linked to genome instability and disease. The main source of aggregation-prone proteins in cells is defective ribosomal products (DRiPs), which are generated by translating ribosomes in the cytoplasm. Here, we report that DRiPs rapidly diffuse into the nucleus and accumulate in nucleoli and PML bodies, two membraneless organelles formed by liquid\u2013liquid phase separation. We show that nucleoli and PML bodies act as dynamic overflow compartments that recruit protein quality control factors and store DRiPs for later clearance. Whereas nucleoli serve as constitutive overflow compartments, PML bodies are stress-inducible overflow compartments for DRiPs. If DRiPs are not properly cleared by chaperones and proteasomes due to proteostasis impairment, nucleoli undergo amyloidogenesis and PML bodies solidify. Solid PML bodies immobilize 20S proteasomes and limit the recycling of free ubiquitin. Ubiquitin depletion, in turn, compromises the formation of DNA repair compartments at fragile chromosomal sites, ultimately threatening cell survival