Problems Affecting Labor

Much experimental work has been devoted in comparing the folding behavior of proteins sharing the same fold but different sequence. The recent design of proteins displaying very high sequence identities but different 3D structure allows the unique opportunity to address the protein-folding problem from a complementary perspective. Here we explored by ℙ-value analysis the pathways of folding of three different heteromorphic pairs, displaying increasingly high-sequence identity (namely, 30%, 77%, and 88%), but different structures called G A (a 3-α helix fold) and G B (an α/β fold). The analysis, based on 132 site-directed mutants, is fully consistent with the idea that protein topology is committed very early along the pathway of folding. Furthermore, data reveals that when folding approaches a perfect two-state scenario, as in the case of the G A domains, the structural features of the transition state appear very robust to changes in sequence composition. On the other hand, when folding is more complex and multistate, as for the G Bs, there are alternative nuclei or accessible pathways that can be alternatively stabilized by altering the primary structure. The implications of our results in the light of previous work on the folding of different members belonging to the same protein family are discussed

Three-point functions in N = 4 Yang-Mills theory and pp-waves

Recently it has been proposed that the coefficient of the three-point function of the BMN operators in = 4 supersymmetric Yang-Mills theory is related to the three-string interactions in the pp-wave background. We calculate three-point functions of these operators to the first order in the effective Yang-Mills coupling λ' = gYM2N/J2 in planar perturbation theory. On the string theory side, we derive the explicit expressions of the Neumann matrices to all orders in 1/(μp+α')2. This allows us to compute the corresponding three-string scattering amplitudes. This provides an all orders prediction for the field theory three-point functions. We compare our field theory results with the string theory results to the subleading order in 1/(μp+α')2 and find perfect agreement

Classical gravitational scattering from a gauge-invariant double copy

We propose a method to compute the scattering angle for classical black hole scattering directly from two massive particle irreducible diagrams in a heavy-mass effective field theory approach to general relativity, without the need of subtracting iteration terms. The amplitudes in this effective theory are constructed using a recently proposed novel colour-kinematic/double copy for tree-level two-scalar, multi-graviton amplitudes, where the BCJ numerators are gauge invariant and local with respect to the massless gravitons. These tree amplitudes, together with graviton tree amplitudes, enter the construction of the required D-dimensional loop integrands and allow for a direct extraction of contributions relevant for classical physics. In particular the soft/heavy-mass expansions of full integrands is circumvented, and all iterating contributions can be dropped from the get go. We use this method to compute the scattering angle up to third post-Minkowskian order in four dimensions, including radiation reaction contributions, also providing the expression of the corresponding integrand in D dimensions

Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment

Foraging behavior of leaf cutting ants: How do workers search for their food?

Forager ants search for adequate food sources in nature and, after their discovery, decide whether the source is suitable or not for the colony. However, we asked “How do workers seek out the substrate for cultivation of the symbiontic fungus on which they feed? To answer this question, we evaluated the distance traveled by individual workers in the search of food and the distance traveled to return to the nest, as well as the time and velocity necessary for these activities. The results showed that the distance traveled by the leaf cutting ant, Atta sexdens rubropilosa (Linneus, 1758), in the search of food was greater than the distance traveled to return with the substrate to the colony. On the other hand, the mean time and velocity were similar for food search and return to the colony. These results support the hypothesis of information transfer, according to which the worker needs to return to the nest at the beginning of foraging to transfer information to other workers and thus to establish the process of worker ant foraging. It can be concluded that workers travel large distances in a random manner until finding their substrate, but the return to the nest is efficient considering the shorter distance traveled.