THE SYNTHESIS, ASSEMBLY, AND SECRETION OF GAMMA GLOBULIN BY MOUSE MYELOMA CELLS : VI. ASSEMBLY OF IGM PROTEINS

The study of the synthesis, assembly, and secretion of IgM by seven murine myeloma tumors has revealed that free mu chain can be detected intracellularly after release from the ribosome. It combines with light chains to form µL. The major intracellular protein in six of the seven tumors was the 8S subunit. One tumor contained considerable amounts of 19S material intracellularly. Those tumors that did not contain 19S IgM intracellulariy appeared to assemble the subunits outside the cell

AID Overlapping and Polη Hotspots Are Key Features of Evolutionary Variation Within the Human Antibody Heavy Chain (IGHV) Genes

© Copyright © 2020 Tang, Bagnara, Chiorazzi, Scharff and MacCarthy. Somatic hypermutation (SHM) of the immunoglobulin variable (IgV) loci is a key process in antibody affinity maturation. The enzyme activation-induced deaminase (AID), initiates SHM by creating C → U mismatches on single-stranded DNA (ssDNA). AID has preferential hotspot motif targets in the context of WRC/GYW (W = A/T, R = A/G, Y = C/T) and particularly at WGCW overlapping hotspots where hotspots appear opposite each other on both strands. Subsequent recruitment of the low-fidelity DNA repair enzyme, Polymerase eta (Polη), during mismatch repair, creates additional mutations at WA/TW sites. Although there are more than 50 functional immunoglobulin heavy chain variable (IGHV) segments in humans, the fundamental differences between these genes and their ability to respond to all possible foreign antigens is still poorly understood. To better understand this, we generated profiles of WGCW hotspots in each of the human IGHV genes and found the expected high frequency in complementarity determining regions (CDRs) that encode the antigen binding sites but also an unexpectedly high frequency of WGCW in certain framework (FW) sub-regions. Principal Components Analysis (PCA) of these overlapping AID hotspot profiles revealed that one major difference between IGHV families is the presence or absence of WGCW in a sub-region of FW3 sometimes referred to as “CDR4.” Further differences between members of each family (e.g., IGHV1) are primarily determined by their WGCW densities in CDR1. We previously suggested that the co-localization of AID overlapping and Polη hotspots was associated with high mutability of certain IGHV sub-regions, such as the CDRs. To evaluate the importance of this feature, we extended the WGCW profiles, combining them with local densities of Polη (WA) hotspots, thus describing the co-localization of both types of hotspots across all IGHV genes. We also verified that co-localization is associated with higher mutability. PCA of the co-localization profiles showed CDR1 and CDR2 as being the main contributors to variance among IGHV genes, consistent with the importance of these sub-regions in antigen binding. Our results suggest that AID overlapping (WGCW) hotspots alone or in conjunction with Polη (WA/TW) hotspots are key features of evolutionary variation between IGHV genes

Exploring Metacognition as a Support for Learning Transfer

The ability to transfer learning to new situations lies at the heart of lifelong learning and the employability of university graduates. Because students are often unaware of the importance of learning transfer and staff do not always explicitly articulate this expectation, this article explores the idea that metacognition (intentional awareness and the use of that awareness) might enhance the development of learning transfer. Our exploratory study includes results from a survey of 74 staff and 118 students from five institutions in Australia, Belgium, UK, and USA. Our data indicate that many staff and a majority of students do not have a clear understanding of what learning transfer entails, and that there are many mismatches between staff and student perceptions, attitudes, and behaviors regarding learning transfer. This helps explain why learning transfer does not occur as often as it could. We found significant positive correlations between thinking about transfer and thinking about learning processes and the likelihood to use awareness to guide practice. These support the idea that metacognition might enhance learning transfer. We offer suggestions for future scholarship of teaching and learning

Reformulating the Schrodinger equation as a Shabat-Zakharov system

We reformulate the second-order Schrodinger equation as a set of two coupled first order differential equations, a so-called "Shabat-Zakharov system", (sometimes called a "Zakharov-Shabat" system). There is considerable flexibility in this approach, and we emphasise the utility of introducing an "auxiliary condition" or "gauge condition" that is used to cut down the degrees of freedom. Using this formalism, we derive the explicit (but formal) general solution to the Schrodinger equation. The general solution depends on three arbitrarily chosen functions, and a path-ordered exponential matrix. If one considers path ordering to be an "elementary" process, then this represents complete quadrature, albeit formal, of the second-order linear ODE.Comment: 18 pages, plain LaTe

Mode regularization of the susy sphaleron and kink: zero modes and discrete gauge symmetry

To obtain the one-loop corrections to the mass of a kink by mode regularization, one may take one-half the result for the mass of a widely separated kink-antikink (or sphaleron) system, where the two bosonic zero modes count as two degrees of freedom, but the two fermionic zero modes as only one degree of freedom in the sums over modes. For a single kink, there is one bosonic zero mode degree of freedom, but it is necessary to average over four sets of fermionic boundary conditions in order (i) to preserve the fermionic Z$_2$ gauge invariance $\psi \to -\psi$, (ii) to satisfy the basic principle of mode regularization that the boundary conditions in the trivial and the kink sector should be the same, (iii) in order that the energy stored at the boundaries cancels and (iv) to avoid obtaining a finite, uniformly distributed energy which would violate cluster decomposition. The average number of fermionic zero-energy degrees of freedom in the presence of the kink is then indeed 1/2. For boundary conditions leading to only one fermionic zero-energy solution, the Z$_2$ gauge invariance identifies two seemingly distinct `vacua' as the same physical ground state, and the single fermionic zero-energy solution does not correspond to a degree of freedom. Other boundary conditions lead to two spatially separated $\omega \sim 0$ solutions, corresponding to one (spatially delocalized) degree of freedom. This nonlocality is consistent with the principle of cluster decomposition for correlators of observables.Comment: 32 pages, 5 figure

A compact statistical model of the song syntax in Bengalese finch

Songs of many songbird species consist of variable sequences of a finite number of syllables. A common approach for characterizing the syntax of these complex syllable sequences is to use transition probabilities between the syllables. This is equivalent to the Markov model, in which each syllable is associated with one state, and the transition probabilities between the states do not depend on the state transition history. Here we analyze the song syntax in a Bengalese finch. We show that the Markov model fails to capture the statistical properties of the syllable sequences. Instead, a state transition model that accurately describes the statistics of the syllable sequences includes adaptation of the self-transition probabilities when states are repeatedly revisited, and allows associations of more than one state to the same syllable. Such a model does not increase the model complexity significantly. Mathematically, the model is a partially observable Markov model with adaptation (POMMA). The success of the POMMA supports the branching chain network hypothesis of how syntax is controlled within the premotor song nucleus HVC, and suggests that adaptation and many-to-one mapping from neural substrates to syllables are important features of the neural control of complex song syntax