Biochemistry of Transglutaminases and Cross-Linking in the Skin

Transglutaminase is a calcium-dependent enzyme found widely in nature. It catalyzes the formation of α-(γ-glutamyl)lysine bonds that participate in processes varying from fibrin clot formation to epidermal cell envelope formation. Epidermal transglutaminase is localized to the granular layer of the epidermis. It catalyzes the covalent cross-linking of a soluble cytoplasmic substrate into large polymers to form the cornified envelope that lines the inner membrane of keratinocytes in the stratum corneum, The soluble precursor from epidermis has been named keratolinin, and from keratinocyte culture, it has been named involucrin. Hair follicle transglutaminase is biochemically and immunochemically distinct from its epidermal counters part. It has been localized to the inner root sheath and medulla of the hair follicle, The substrate of hair follicle transglutaminase has been poorly defined but appears to be rich in the amino acid citrulline, Transglutaminase has been shown to be an important marker of normal differentiation. There is a rise in its activity at the time of keratinization, and transglutaminase activity has been shown to be greatly decreased in basal cell epithelioma and in psoriasis. Keratinocyte cell culture has proven most helpful in delineating the processes of normal differentiation and keratinization, since the formation of the cell envelope in culture appears to parallel the formation in vivo

Effects of alternation in some quasi‐one‐dimensional magnetic materials

Exchange coupling in Cu(II) and Mn(III) compounds with unusual structures is discussed. {[Cu(bipyrimidine)(OH)(H2O)] (ClO4)}n has an alternatingly bridged structure with alternating ferromagnetic (+167.6 cm−1 through the hydroxo bridge) and antiferromagnetic (−79.8 cm−1 through the bipyrimidine bridge) interactions. Copper(II) phthalate monohydrate has alternating next‐nearest‐neighbor exchange with J=−12.3 cm−1 and α=0.06. This is the first member of this class. The compound K2[Mn(III) (salicylate)2][Mn(III) (salicylate)2]{CH3OH]2 has manganese ions in two environments alternating along the chain. A modified model for the chain is presented, and exchange coupling is found to be small since magnetic orbitals are not linked by the bridging ligand.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70701/2/JAPIAU-69-8-6013-1.pd

Primary Caregivers of Children Affected by Disorders of Sex Development: Mental Health and Caregiver Characteristics in the Context of Genital Ambiguity and Genitoplasty

Purpose. To determine the relationship between having a child with a DSD including ambiguous external genitalia, as well as the decision of whether or not to have early genitoplasty for that child, on the mental health and parenting characteristics of caregivers. Materials and Methods. Caregivers were recruited from centers that specialize in DSD medicine and completed the Beck Depression Inventory 2nd Edition (BDI-2), Beck Anxiety Index (BAI), Parent Protection Scale (PPS), Child Vulnerability Scale (CVS) and Parenting Stress Index/Short Form (PSI/SF). Results and Conclusions. Sixty-eight caregivers provided informed consent and completed the study. Among female caregivers whose children never received genitoplasty, greater parenting stress was reported (F(1, 40) = 5.08, p = .03). For male caregivers, those whose children received genitoplasty within the first year of life reported more overprotective parenting and parenting stress than those whose children received genitoplasty later than 12 months of age (F(1, 13) = 6.16, p = 0.28); F(1, 15) = 6.70, p = .021), respectively)

Conditional müller cell ablation causes independent neuronal and vascular pathologies in a novel transgenic model

Müller cells are the major glia of the retina that serve numerous functions essential to retinal homeostasis, yet the contribution of Müller glial dysfunction to retinal diseases remains largely unknown. We have developed a transgenic model using a portion of the regulatory region of the retinaldehyde binding protein 1 gene for conditional Müller cell ablation and the consequences of primary Müller cell dysfunction have been studied in adult mice. We found that selective ablation of Müller cells led to photoreceptor apoptosis, vascular telangiectasis, blood-retinal barrier breakdown and, later, intraretinal neovascularization. These changes were accompanied by impaired retinal function and an imbalance between vascular endothelial growth factor-A (VEGF-A) and pigment epithelium-derived factor. Intravitreal injection of ciliary neurotrophic factor inhibited photoreceptor injury but had no effect on the vasculopathy. Conversely, inhibition of VEGF-A activity attenuated vascular leak but did not protect photoreceptors. Our findings show that Müller glial deficiency may be an important upstream cause of retinal neuronal and vascular pathologies in retinal diseases. Combined neuropro-tective and anti-angiogenic therapies may be required to treat Müller cell deficiency in retinal diseases and in other parts of the CNS associated with glial dysfunction

Expressions 1980

Expressions contains selected work from the 1980 Creative Writing Contest winners and honorable mentions, Campus Chronicle Photography Contest entrants, and the Commercial Art students at Des Moines Area Community College. Design, typography and layout was done by Journalism students.https://openspace.dmacc.edu/expressions/1002/thumbnail.jp

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

JWST reveals a possible z∼11z \sim 11 galaxy merger in triply-lensed MACS0647−-JD

MACS0647$-$JD is a triply-lensed $z\sim11$ galaxy originally discovered with the Hubble Space Telescope. Here we report new JWST imaging, which clearly resolves MACS0647$-$JD as having two components that are either merging galaxies or stellar complexes within a single galaxy. Both are very small, with stellar masses $\sim10^8\,M_\odot$ and radii $r<100\,\rm pc$. The brighter larger component "A" is intrinsically very blue ($\beta\sim-2.6$), likely due to very recent star formation and no dust, and is spatially extended with an effective radius $\sim70\,\rm pc$. The smaller component "B" appears redder ($\beta\sim-2$), likely because it is older ($100-200\,\rm Myr$) with mild dust extinction ($A_V\sim0.1\,\rm mag$), and a smaller radius $\sim20\,\rm pc$. We identify galaxies with similar colors in a high-redshift simulation, finding their star formation histories to be out of phase. With an estimated stellar mass ratio of roughly 2:1 and physical projected separation $\sim400\,\rm pc$, we may be witnessing a galaxy merger 400 million years after the Big Bang. We also identify a candidate companion galaxy C $\sim3\,{\rm kpc}$ away, likely destined to merge with galaxies A and B. The combined light from galaxies A+B is magnified by factors of $\sim$8, 5, and 2 in three lensed images JD1, 2, and 3 with F356W fluxes $\sim322$, $203$, $86\,\rm nJy$ (AB mag 25.1, 25.6, 26.6). MACS0647$-$JD is significantly brighter than other galaxies recently discovered at similar redshifts with JWST. Without magnification, it would have AB mag 27.3 ($M_{UV}=-20.4$). With a high confidence level, we obtain a photometric redshift of $z=10.6\pm0.3$ based on photometry measured in 6 NIRCam filters spanning $1-5\rm\mu m$, out to $4300\,\r{A}$ rest-frame. JWST NIRSpec observations planned for January 2023 will deliver a spectroscopic redshift and a more detailed study of the physical properties of MACS0647$-$JD.Comment: 27 pages, 14 figures, submitted to Natur

spatially-explicit test of the refuge strategy for delaying insecticide resistance

The refuge strategy is used worldwide to delay the evolution of pest resistance to insecticides that are either sprayed or produced by transgenic Bacillus thuringiensis (Bt) crops. This strategy is based on the idea that refuges of host plants where pests are not exposed to an insecticide promote survival of susceptible pests. Despite widespread adoption of this approach, large-scale tests of the refuge strategy have been problematic. Here we tested the refuge strategy with 8 y of data on refuges and resistance to the insecticide pyriproxyfen in 84 populations of the sweetpotato whitefly (Bemisia tabaci) from cotton fields in central Arizona. We found that spatial variation in resistance to pyriproxyfen within each year was not affected by refuges of melons or alfalfa near cotton fields. However, resistance was negatively associated with the area of cotton refuges and positively associated with the area of cotton treated with pyriproxyfen. A statistical model based on the first 4 y of data, incorporating the spatial distribution of cotton treated and not treated with pyriproxyfen, adequately predicted the spatial variation in resistance observed in the last 4 y of the study, confirming that cotton refuges delayed resistance and treated cotton fields accelerated resistance. By providing a systematic assessment of the effectiveness of refuges and the scale of their effects, the spatially explicit approach applied here could be useful for testing and improving the refuge strategy in other crop-pest systems. pesticide resistance | predictive evolutionary models | pest management | resistance management P opulation growth will continue to favor agricultural intensification for decades. Because agricultural intensification is associated with increased pest pressure, pesticides generally help to increase yield (1-3). Although significant progress has been made to reduce reliance on pesticides (4, 5), an increasing number of insects and mites exhibit field-evolved resistance to synthetic pesticides, Bacillus thuringiensis (Bt) sprays, and transgenic Bt crops (6, 7). Negative consequences of resistance include increased pesticide use, disruption of food webs and ecosystem services, increased risk to human health, and loss of profits for farmers and industry (1, 3). One of the main strategies for delaying resistance promotes survival of susceptible pests by providing refuges, which are areas of host plants where pests are not exposed to an insecticide. Theory predicts that refuges will slow the evolution of resistance by reducing the fitness advantage of resistant individuals (7-9). Refuges can also reduce the heritability of resistance when susceptible individuals mate with resistant individuals surviving exposure to an insecticide (7). Empirical support for the refuge strategy was provided by short-term laboratory and greenhouse experiments (10, 11). Although these experiments test the hypothesis that mating between susceptible and resistant individuals delays the evolution of resistance, they do not consider several factors that affect resistance in the field (7-9), and thus only provide partial support for effectiveness of the refuge strategy in the field. Retrospective analyses of variation in resistance evolution in the field also suggest that refuges have been effective, but these previous tests have been based primarily on comparisons among species, or qualitative comparisons within species based on a limited number of widely separated geographic areas (12, 13). In such tests, factors that vary among species or geographic areas can confound the effects of refuges. Accordingly, large-scale field tests of the refuge strategy for a single species within a geographic area where factors affecting resistance are similar are needed to test the refuge strategy more rigorously. Moreover, tests of predictive refuge strategy models are required to determine if the refuge strategy can delay resistance (14). Furthermore, to improve our ability to develop efficient refuge strategies, empirical approaches are necessary to characterize effects of refuges on resistance evolution (7, 15). Here we tested the refuge strategy using 8 y of data on refuges and resistance to the insecticide pyriproxyfen in 84 populations of the sweetpotato whitefly (Bemisia tabaci) sampled in cotton fields of central Arizona. We studied the B biotype of B. tabaci, also known as the Asia Minor-Middle East 1 species, which is a key pest of cotton and other crops in Arizona and worldwide (16). The insect growth regulators pyriproxyfen (a juvenile hormone analog) and buprofezin (a chitin synthesis inhibitor) are selective insecticides that have been used for whitefly control in Arizona cotton (Gossypium spp.) since 1996 (17, 18). A single application of either insecticide on cotton when B. tabaci populations start to increase has substantially reduced sprays of broad-spectrum insecticides, helped to conserve natural enemies, and restored farmers &apos; profits (18, 19). To deter rapid evolution of resistance, farmers in Arizona generally have not used pyriproxyfen to control B. tabaci on crops other than cotton Although B. tabaci is polyphagous, few whitefly crops other than cotton are available in central Arizona from June to September, when pyriproxyfen is sprayed on cotton. In principle, crops that could act as refuges include spring melons (Citrullus lanatus and Cucumis melo), alfalfa (Medicago sativa) and cotton not treated with pyriproxyfen (referred to hereafter as untreated cotton). B. tabac