Evolution of antigen binding receptors

This review addresses issues related to the evolution of the complex multigene families of antigen binding receptors that function in adaptive immunity. Advances in molecular genetic technology now permit the study of immunoglobulin (Ig) and T cell receptor (TCR) genes in many species that are not commonly studied yet represent critical branch points in vertebrate phylogeny. Both Ig and TCR genes have been defined in most of the major lineages of jawed vertebrates, including the cartilaginous fishes, which represent the most phylogenetically divergent jawed vertebrate group relative to the mammals. Ig genes in cartilaginous fish are encoded by multiple individual loci that each contain rearranging segmental elements and constant regions. In some loci, segmental elements are joined in the germline, i.e. they do not undergo genetic rearrangement. Other major differences in Ig gene organization and the mechanisms of somatic diversification have occurred throughout vertebrate evolution. However, relating these changes to adaptive immune function in lower vertebrates is challenging. TCR genes exhibit greater sequence diversity in individual segmental elements than is found in Ig genes but have undergone fewer changes in gene organization, isotype diversity, and mechanisms of diversification. As of yet, homologous forms of antigen binding receptors have not been identified in jawless vertebrates; however, acquisition of large amounts of structural data for the antigen binding receptors that are found in a variety of jawed vertebrates has defined shared characteristics that provide unique insight into the distant origins of the rearranging gene systems and their relationships to both adaptive and innate recognition processes

Small Business Management: Using Assessment to Help Millennials Bridge the Gap Between the Classroom and Reality

The purpose of this paper is to explore students’ perceptions of entrepreneurship as a career path and match those perceptions with academic program assessment in an effort to help academic departments better prepare students for careers in small business management. As this is exploratory research, this paper employs methods that capture a broad perspective, collecting data from multiple sources over the last decade. Data obtained from multiple sources allows for a meaningful and thought-provoking discussion on methods academic departments can use to help prepare students for success. Additionally, the data, analysis, and discussion help inform academic professionals charged with making decisions about academic programming in this area. This paper also increases understanding of the entrepreneurial intentions of contemporary undergraduates (mostly millennials) and provides some encouragement, guidance, and lessons learned for academic departments, which are increasingly involved in assessment of academic programs and student learning. In the conclusion, we review the approach taken by one university in response to issues identified through assessment

A Comparison of X-ray and Radio Emission from the Supernova Remnant Cassiopeia A

We compare the radio and soft X-ray brightness as a function of position within the young supernova remnant Cassiopeia A. A moderately strong correlation (r = 0.7) was found between the X-ray emission (corrected for interstellar absorption) and radio emission, showing that the thermal and relativistic plasmas occupy the same volumes and are regulated by common underlying parameters. The logarithmic slope of the relationship, ln(Sx-ray) = 1.2 x Sradio + ln(k) implies that the variations in brightness are primarily due to path length differences. The X-ray and radio emissivities are both high in the same general locations, but their more detailed relationship is poorly constrained and probably shows significant scatter. The strongest radio and X-ray absorption is found at the western boundary of Cas A. Based on the properties of Cas A and the absorbing molecular cloud, we argue that they are physically interacting. We also compare ASCA derived column densities with 21 cm H I and 18 cm OH optical depths in the direction of Cas A, in order to provide an independent estimate of ISM properties. We derive an average value for the H I spin temperature of about 40 K and measure the ratio of OH to molecular hydrogen to be nominally larger than previous estimates. Keywords: Cas A, Cassiopeia A, interstellar medium, molecular clouds, radio astronomy, supernova remnants, X-ray astronomyComment: To appear in Vol. 446 of The Astrophysical Journal on Aug. 1, 1996; 10 pages with 5 embedded figures; replaced because of updated reference

Strong variation in weathering of layered rock maintains hillslope‐scale strength under high precipitation

The evolution of volcanic landscapes and their landslide potential are both dependent upon the weathering of layered volcanic rock sequences. We characterize critical zone structure using shallow seismic Vp and Vs profiles and vertical exposures of rock across a basaltic climosequence on Kohala peninsula, Hawai’i, and exploit the dramatic gradient in mean annual precipitation (MAP) across the peninsula as a proxy for weathering intensity. Seismic velocity increases rapidly with depth and the velocity–depth gradient is uniform across three sites with 500–600 mm/yr MAP, where the transition to unaltered bedrock occurs at a depth of 4 to 10 m. In contrast, velocity increases with depth less rapidly at wetter sites, but this gradient remains constant across increasing MAP from 1000 to 3000 mm/yr and the transition to unaltered bedrock is near the maximum depth of investigation (15–25 m). In detail, the profiles of seismic velocity and of weathering at wet sites are nowhere monotonic functions of depth. The uniform average velocity gradient and the greater depths of low velocities may be explained by the averaging of velocities over intercalated highly weathered sites with less weathered layers at sites where MAP > 1000 mm/yr. Hence, the main effect of climate is not the progressive deepening of a near‐surface altered layer, but rather the rapid weathering of high permeability zones within rock subjected to precipitation greater than ~1000 mm/yr. Although weathering suggests mechanical weakening, the nearly horizontal orientation of alternating weathered and unweathered horizons with respect to topography also plays a role in the slope stability of these heterogeneous rock masses. We speculate that where steep, rapidly evolving hillslopes exist, the sub‐horizontal orientation of weak/strong horizons allows such sites to remain nearly as strong as their less weathered counterparts at drier sites, as is exemplified by the 50°–60° slopes maintained in the amphitheater canyons on the northwest flank of the island. Copyright © 2017 John Wiley & Sons, Ltd.Seismic velocity profiles across a basalt climosequence in Hawai’i reveal that above a particular precipitation threshold, rapid weathering of high‐permeability layers produces intercalated low‐velocity horizons and dramatically lowers the average seismic velocity of the rock section. However, less permeable layers remain relatively unweathered and thus still contribute significantly to the mechanical competence of the profile, which may explain maintenance of steep‐walled canyons under high precipitation rates. Such observations challenge a top‐down model of progressive weathering (i.e. weakening) of the substrate and therefore suggest that high strength can be maintained even under high precipitation rates, if horizontally layered horizons of different weathering potential exist.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143701/1/esp4290.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143701/2/esp4290_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143701/3/esp4290-sup-0001-SupplementaFiles_FINAL.pd

Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons.

The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed. To investigate their properties, we isolated glia and neurons from Cln3-deficient mice and studied their basic biology in culture. Upon stimulation, both Cln3-deficient astrocytes and microglia also showed an attenuated ability to transform morphologically, and an altered protein secretion profile. These defects were more pronounced in astrocytes, including the reduced secretion of a range of neuroprotective factors, mitogens, chemokines and cytokines, in addition to impaired calcium signalling and glutamate clearance. Cln3-deficient neurons also displayed an abnormal organization of their neurites. Most importantly, using a co-culture system, Cln3-deficient astrocytes and microglia had a negative impact on the survival and morphology of both Cln3-deficient and wildtype neurons, but these effects were largely reversed by growing mutant neurons with healthy glia. These data provide evidence that CLN3 disease astrocytes are functionally compromised. Together with microglia, they may play an active role in neuron loss in this disorder and can be considered as potential targets for therapeutic interventions