Antimicrobial peptides: agents of border protection for companion animals.

Over the past 20 years, there have been significant inroads into understanding the roles of antimicrobial peptides in homeostatic functions and their involvement in disease pathogenesis. In addition to direct antimicrobial activity, these peptides participate in many cellular functions, including chemotaxis, wound healing and even determination of canine coat colour. Various biological and genetic approaches have helped to elucidate the role of antimicrobial peptides with respect to innate immunity and host defense. Associations of antimicrobial peptides with various skin diseases, including psoriasis, rosacea and atopic dermatitis, have been documented in humans. In the longer term, therapeutic modulation of antimicrobial peptide expression may provide effective new treatments for disease. This review highlights current knowledge about antimicrobial peptides of the skin and circulating leukocytes, with particular focus on relevance to physiology and disease in companion animals

Transition-metal silicides formed by ion mixing and by thermal annealing: Which species moves?

The moving species during the formation of Pt2Si, Ni2Si, and CrSi2 by both ion mixing with 300–600 keV Xe ions and thermal annealing is identified with inert markers using backscattering spectrometry. Samples of metal-on-silicon and silicon-on-metal have been used, evaporated on SiO2 substrates with two very thin markers (Mo for Pt2Si, W for Ni2Si and CrSi2) placed at the metal–silicon interface, and at the bottom interface with the SiO2 substrate. Monitoring the separation of the two markers as a function of the amount of silicide formed determines the ratio of atomic transport through the growing silicide layer. The results establish that the dominant moving species in both silicide formation processes is the same for the refractory metal-silicide CrSi2, e.g., Si, whereas different atomic transport ratios are found in the case of the near-noble metal silicides Pt2Si and Ni2Si. This outcome is discussed in terms of high-temperature effects during thermal formation of transition-metal silicides

Sputtered W–N diffusion barriers

The thermal stability of reactively sputtered tungsten–nitrogen alloy thin films is investigated for the application as diffusion barriers in silicon contact metallizations. The composition of W–N barriers is varied over a wide range including pure W. Aluminum, gold, and silver are used as low resistivity overlayers. Metallurgical interactions at temperatures ranging from 500 to 900 °C are studied. Incorporating nitrogen into tungsten advantageously stabilizes all three systems. The overall failure takes place rapidly above critical temperatures that depend on both the metal overlayer and the microstructure of the barrier. In some cases, W–N alloys can effectively prevent interdiffusion at temperatures as high as 800 °C for 30 min

A de novo variant in the keratin 1 gene (KRT1) in a Chinese shar-pei dog with severe congenital cornification disorder and non-epidermolytic ichthyosis.

A 3-months old Chinese shar-pei puppy with ichthyosis was investigated. The dog showed generalized scaling, alopecia and footpad lesions. Histopathological examinations demonstrated a non-epidermolytic hyperkeratosis. The parents of the affected puppy did not show any skin lesions. A trio whole genome sequencing analysis identified a heterozygous de novo 3 bp deletion in the KRT1 gene in the affected dog. This variant, NM_001003392.1:c.567_569del, is predicted to delete a single asparagine from the conserved coil 1A motif within the rod domain of KRT1, NP_001003392.1:p.(Asn190del). Immunohistochemistry demonstrated normal levels of KRT1 expression in the epidermis and follicular epithelia. This might indicate that the variant possibly interferes with keratin dimerization or another function of KRT1. Missense variants affecting the homologous asparagine residue of the human KRT1 cause epidermolytic hyperkeratosis. Histologically, the investigated Chinese shar-pei showed a non-epidermolytic ichthyosis. The finding of a de novo variant in an excellent functional candidate gene strongly suggests that KRT1:p.Asn190del caused the ichthyosis phenotype in the affected Chinese shar-pei. To the best of our knowledge, this is the first description of a KRT1-related non-epidermolytic ichthyosis in domestic animals

Laser annealing of silicon on sapphire

Silicon-implanted silicon-on-sapphire wafers have been annealed by 50-ns pulses from a Q-switched Nd : YAG laser. The samples have been analyzed by channeling and by omega-scan x-ray double diffraction. After irradiation with pulses of a fluence of about 5 J cm^–2 the crystalline quality of the silicon layer is found to be better than in the as-grown state

SOAT1 missense variant in two cats with sebaceous gland dysplasia.

Spontaneously arisen hereditary diseases in domestic animals provide an excellent opportunity to study the physiological functions of the altered genes. We investigated two 4-month-old sibling domestic short haired kittens with dry dark debris around the eyes, nose, and ears, dark crusting on the legs and a thin poor hair coat. Skin biopsies revealed abnormal sebaceous gland morphology with lack of normal sebocyte arrangement and differentiation. Hair follicles had a distorted silhouette, interpreted as a change secondary to the observed sebaceous gland dysplasia. Whole genome sequencing on both affected kittens and 65 genetically diverse feline genomes was performed. Filtering for variants that were present in both kittens but absent from the control genomes revealed a homozygous missense variant in SOAT1, encoding sterol O-acyltransferase 1. The protein is localized in the endoplasmic reticulum and catalyzes the formation of cholesteryl esters, an essential component of sebum and meibum. The identified SOAT1:c.1531G > A variant is predicted to change a highly conserved glycine residue within the last transmembrane domain of SOAT1, p.Gly511Arg. In mice, variants in Soat1 or complete knockout of the gene lead to the "hair interior defect" (hid) or abnormal Meibomian glands, respectively. SOAT1:c.1531G > A represents a plausible candidate variant for the observed sebaceous gland dysplasia in both kittens of this study. The variant was not present in 10 additional cats with a similar clinical and histopathological phenotype suggesting genetic heterogeneity. SOAT1 variants should be considered as potential cause in hereditary sebaceous gland dysplasias of humans and domestic animals

Mal/SRF Is Dispensable for Cell Proliferation in Drosophila

The Mal/SRF transcription factor is regulated by the level of G-actin in cells and has important roles in cell migration and other actin-dependent processes in Drosophila. A recent report suggests that Mal/SRF and an upstream regulator, Pico, are required for cell proliferation and tissue growth in Drosophila. I find otherwise. Mutation of Mal or SRF does not affect cell proliferation in the fly wing. Furthermore, I cannot reproduce the reported effects of Pico RNAi or Pico overexpression on body size. Nevertheless, I can confirm that overexpression of Pico or Mal causes tissue overgrowth specifically in the fly wing - where SRF is most highly expressed. My results indicate that Mal/SRF can promote tissue growth when abnormally active, but is not normally required for tissue growth during development

Examination of Fluconazole-Induced Alopecia in an Animal Model and Human Cohort.

Fluconazole-induced alopecia is a significant problem for patients receiving long-term therapy. We evaluated the hair cycle changes of fluconazole in a rat model and investigated potential molecular mechanisms. Plasma and tissue levels of retinoic acid were not found to be causal. Human patients with alopecia attributed to fluconazole also underwent detailed assessment and in both our murine model and human cohort fluconazole induced telogen effluvium. Future work further examining the mechanism of fluconazole-induced alopecia should be undertaken

Variable response in alpine tree-ring stable isotopes following volcanic eruptions in the tropics and iceland

The importance of the stable isotopes in tree rings for the study of the climate variations caused by volcanic eruptions is still unclear. We studied δ18O, δD, δ13C stable isotopes of larch and cembran pine cellulose around four major eruptions with annual resolution, along with a superposed epoch analysis of 34 eruptions with 5-year resolution. Initial analysis of the tropical Tambora (1815 CE) and Samalas (1257 CE) eruptions showed a post-eruption decrease in δ18O values attributed to post-volcanic cooling and increased summer precipitation in Southern Europe, as documented by observations and climate simulations. The post-volcanic cooling was captured by the δD of speleothem fluid inclusion. The δ18O decrease was also observed in the analysis of 34 major tropical eruptions over the last 2000 years. In contrast, the eruptions of c. 750, 756, and 764 CE attributed to Icelandic volcanoes left no significant responses in the cellulose isotopes. Further analysis of all major Icelandic eruptions in the last 2000 years showed no consistent isotopic fingerprints, with the exception of lower post-volcanic δ13C values in larch. In summary, the δ18O values of cellulose can provide relevant information on climatic and hydroclimatic variations following major tropical volcanic eruptions, even when using the 5-year resolution wood samples of the Alpine Tree-Ring Isotope Record database