526 research outputs found
Perception of limb orientation in the vertical plane depends on center of mass rather than inertial eigenvectors
We performed two experiments to test the hypothesis that the perception of limb orientation depends on inertial eigenvectors (
Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation
Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration
Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.
Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage
Simulating the seeder–feeder impacts on cloud ice and precipitation over the Alps
The ice phase impacts many cloud properties as well as cloud lifetime. Ice particles that sediment into a lower cloud from an upper cloud (external seeder–feeder process) or into the mixed-phase region of a deep cloud from cirrus levels (internal seeder–feeder process) can influence the ice phase of the lower cloud, amplify cloud glaciation and enhance surface precipitation. Recently, numerical weather prediction modeling studies have aimed at representing the ice crystal number concentration in mixed-phase clouds more accurately by including secondary ice formation processes. The increase in the ice crystal number concentration can impact the number of ice particles that sediment into the lower cloud and alter its composition and precipitation formation. In the Swiss Alps, the orography permits the formation of orographic clouds, making it ideal for studying the occurrence of multi-layered clouds and the seeder–feeder process. We present results from a case study on 18 May 2016, showing the occurrence frequency of multi-layered clouds and the seeder–feeder process. About half of all observed clouds were categorized as multi-layered, and the external seeder–feeder process occurred in 10 % of these clouds. Between cloud layers, ≈60 % of the ice particle mass was lost due to sublimation or melting. The external seeder–feeder process was found to be more important than the internal seeder–feeder process with regard to the impact on precipitation. In the case where the external seeder–feeder process was inhibited, the average surface precipitation and riming rate over the domain were both reduced by 8.5 % and 3.9 %, respectively. When ice–graupel collisions were allowed, further large reductions were seen in the liquid water fraction and riming rate. Inhibiting the internal seeder–feeder process enhanced the liquid water fraction by 6 % compared to a reduction of 5.8 % in the cloud condensate, therefore pointing towards the de-amplification in cloud glaciation and a reduction in surface precipitation. Adding to the observational evidence of frequent seeder–feeder situations, at least over Switzerland, our study highlights the extensive influence of sedimenting ice particles on the properties of feeder clouds as well as on precipitation formation.</p
Educationalization of Social Problems and the Educationalization of the Modern World
The catchword ‘educationalization,’ which enjoyed some popularity around 1920, has been used increasingly since the 1980s, first in the German and then in the Belgian and English discussions. Although the uses of and intentions behind the term are far from identical, they all express a perceived intersection between distinct social practices, one of which is education. As a rule, this intersection is interpreted as assigning education the task of coping with perceived social problems. Accordingly, the most popular expression of this mode of thought has been labeled, in an abstracting way, the educationalization of social problems. This entry builds on that but suggests a more comprehensive view, less reactive in character, by claiming that since the 18th century, the construction of modernity, progress, and open future depends on an idea of education that promises to be the engine of modernity by means of (new) and broadly disseminated knowledge and technologies and, at the same time, an instance of moral reassurance empowering the individual exposed to these modern conditions and their moral hazards to act morally or virtuously. Educationalization of the modern world, in this more comprehensive way, is a key concept for understanding and deciphering the grand narratives of modernity and the modern self
Specific binding of a hexanucleotide to HIV-1 reverse transcriptase: a novel class of bioactive molecules
Short oligonucleotides below 8–10 nt in length adopt relatively simple structures. Accordingly, they represent interesting and so far unexplored lead compounds as molecular tools and, potentially, for drug development as a rational improvement of efficacy seem to be less complex than for other classes of longer oligomeric nucleic acid. As a ‘proof of concept’, we describe the highly specific binding of the hexanucleotide UCGUGU (Hex-S3) to human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) as a model target. Ultraviolet (UV) cross-linking studies and competition experiments with primer/template substrates and a RT-directed aptamer suggest site-specific binding of Hex-S3 to the large subunit (p66) of the viral enzyme. The affinity of 5.3 μM is related to hexanucleotide-specific suppression of HIV-1 replication in human cells by up to three orders of magnitude indicating that Hex-S3 exerts specific and biologically relevant activity. Experimental evidence described here further suggests a systematic hexamer array-based search for new tools for molecular biology and novel lead compounds in nucleic acid-based drug development
National Rugby League athletes and tendon tap reflex assessment: a matched cohort clinical study
- …
