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Additional file 1: Figure S1. Comparison of circadian genes identified from longitudinal dermis and epidermis samples. Figure S2. MetaCycle predicted phases of ARNTL, melatonin and cortisol in epidermis and dermis for 20 participants. Figure S3. Evaluation of circadian clock robustness in epidermis and dermis across different body sites. Figure S4. Phase order of identified clock and clock-associated genes from epidermis and dermis. Figure S5. The relative phase to ARNTL matches relative phase to melatonin or cortisol for time-stamped samples in epidermis and dermis. Figure S6. The pipeline of identifying and testing dermal candidate biomarkers using ZeitZeiger. Figure S7. Candidate biomarkers for predicting molecular clock phase of a single dermal sample. Figure S8. Prediction accuracy of candidate biomarkers from epidermis and dermis. Figure S9. Three steps of running SkinPhaser. Table S1. The list of skin datasets used in this study. Table S2. The list of software packages used in this study.

Supplemental material, Supporting_information_manucript_TECH-19-0066 for O-Benzylhydroxylamine (BHA) as a Cleavable Tag for Isolation and Purification of Reducing Glycans by Ying Zhang, Yuyang Zhu, Yi Lasanajak, David F. Smith and Xuezheng Song in SLAS Technology

The murine CLEC4f gene encodes the Kupffer cell receptor, a galactose-binding receptor containing a C-type carbohydrate-recognition domain. Orthologs have been identified in nearly 100 species. The receptors from rat and mouse have previously been characterized and data presented here show that functional CLEC4f protein is expressed in domestic cattle (Bos taurus). However, the human CLEC4f gene does not encode a functional receptor because a mutation in the splice acceptor site of the final exon prevents appropriate splicing and a missense mutation disrupts the sugar-binding site. Transcriptomic and PCR analysis of transcripts confirms the absence of a spliced transcript containing the final exon and only background levels of transcripts are detected in human tissues. These mutations are also present in the CLEC4f gene in Neanderthals. In contrast to humans, closely related species, including chimpanzees, do have CLEC4f genes that encode full-length receptors. Affinity chromatography and glycan array results demonstrate that the chimpanzee, bovine and murine proteins all bind to galactose, but they show preferences for different subsets of galactose-containing glycans. In non-human primates, the receptor is expressed in spleen rather than in liver. The results indicate that the CLEC4f protein probably has distinct functions in different species. Absence of the receptor precludes using it for targeting of glycoconjugates to cells in human liver. The fact that CLEC4f protein is expressed in spleen in non-human primates and the close evolutionary relationship of the CLEC4f protein to langerin (CD207) suggest that it may function in the immune system, possibly as a pathogen receptor.

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Knowledge of lectin and glycosidase specificities is fundamental to the study of glycobiology. The primary specificities of such molecules can be uncovered using well-established tools, but the complex details of their specificities are difficult to determine and describe. Here we present a language and algorithm for the analysis and description of glycan motifs with high complexity. The language uses human-readable notation and wildcards, modifiers, and logical operators to define motifs of nearly any complexity. By applying the syntax to the analysis of glycan-array data, we found that the lectin AAL had higher binding where fucose groups are displayed on separate branches. The lectin SNA showed gradations in binding based on the length of the extension displaying sialic acid and on characteristics of the opposing branches. A new algorithm to evaluate changes in lectin binding upon treatment with exoglycosidases identified the primary specificities and potential fine specificities of an α1-2-fucosidase and an α2-3,6,8-neuraminidase. The fucosidase had significantly lower action where sialic acid neighbors the fucose, and the neuraminidase showed statistically lower action where α1-2 fucose neighbors the sialic acid or is on the opposing branch. The complex features identified here would have been inaccessible to analysis using previous methods. The new language and algorithms promise to facilitate the precise determination and description of lectin and glycosidase specificities.

International audience; Ficolins are oligomeric innate immune recognition proteins consisting of a collagen-like region and a fibrinogen-like recognition domain that bind to pathogen- and apoptotic cell-associated molecular patterns. To investigate their carbohydrate binding specificities, serum-derived L-ficolin and recombinant H- and M-ficolins were fluorescently labeled, and their carbohydrate binding ability was analyzed by glycan array screening. L-ficolin preferentially recognized disulfated N-acetyllactosamine and tri- and tetrasaccharides containing terminal galactose or N-acetylglucosamine. Binding was sensitive to the position and orientation of the bond between N-acetyllactosamine and the adjacent carbohydrate. No significant binding of H-ficolin to any of the 377 glycans probed could be detected, providing further evidence for its poor lectin activity. M-ficolin bound preferentially to 9-O-acetylated 2-6-linked sialic acid derivatives and to various glycans containing sialic acid engaged in a 2-3 linkage. To further investigate the structural basis of sialic acid recognition by M-ficolin, point mutants were produced in which three residues of the fibrinogen domain were replaced by their counterparts in L-ficolin. Mutations G221F and A256V inhibited binding to the 9-O-acetylated sialic acid derivatives, whereas Y271F abolished interaction with all sialic acid-containing glycans. The crystal structure of the Y271F mutant fibrinogen domain was solved, showing that the mutation does not alter the structure of the ligand binding pocket. These analyses reveal novel ficolin ligands such as sulfated N-acetyllactosamine (L-ficolin) and gangliosides (M-ficolin) and provide precise insights into the sialic acid binding specificity of M-ficolin, emphasizing the essential role of Tyr(271) in this respect.

The study is initially concerned with the origins and development of different approaches to nutrition science in Britain during the first three decades of the twentieth century. The contrasting approaches are shown to embody alternative "styles of thought" in the sense used by Karl Mannheim. An account of the work of the Advisory Committee on Nutrition of the Ministry of Health (founded 1931) is then given. The conflicts which occured during the deliberations of the Committee are interpreted as conflicts between those who advanced the contrasting "styles of thought." The focus of attention then shifts to the foundation and development of the Nutrition Society (1941). The disputes which occured in the Nutrition Society during its early years are shown to be largely concerned with alternative notions of the application of nutritional knowledge. Developments in the Society after the war, it is suggested, must be understood against the background of the post -war reaction against the "social relations of science movement ". The foundation of the first Nutrition Degree in 1953 at the Nutrition Department at Queen Elizabeth College of the University of London, is then considered. A hypothesis is presented which suggests an explanation of certain important features of the professional ideology of nutrition which has been associated with the College.

This study compares financially optimal uneven-aged and even-aged silvicultural regimes of loblolly pine (Pinus Taeda). Uneven-aged regimes which maximize net present value (NPV) are found by quantifying the effects of diameter distribution (Q factor), maximum diameter, cutting cycle, and residual basal area on NPV. For the benchmark inputs, the regime yielding the highest NPV had a maximum diameter of 12 inches, residual basal area of 45 ft²/acre, and a cutting cycle of 11 years. Financially optimal even-aged regimes are taken from published literature of even-aged silviculture. Even-aged and uneven-aged silvicultural regimes are simulated starting from, 1) bare land, 2) a balanced uneven-aged loblolly pine stand, and 3) a mature even-aged loblolly pine stand. For the three starting conditions and selected benchmark variable values, simulation of even-aged silviculture yields NPVs of $877, $2,152 and $3,400 per acre and simulation of uneven-aged silviculture yields NPVs of $644, $2,084, and $2,569 per acre. Sensitivity analysis shows, for the levels of the variables tested, that even-aged silviculture yields higher NPVs than uneven-aged silviculture when starting from bare land or from a mature even-aged stand. When starting from an uneven-aged stand, for the variable values tested, uneven and even-aged silviculture are financially very competitive. Aside from the aesthetic benefits of avoiding clearcutting under uneven-aged silviculture, non-timber considerations between loblolly pine silvicultural systems are not well documented. Resource professionals hold opinions often in direct conflict with each other regarding the non-timber costs and benefits of even-aged and uneven-aged silviculture when considering wildlife, soil and water, and catastrophic damage events. Master of Science

The lipid in milk (milk fat) is found in the form of droplets known as milk lipid globules (MLG). These milk lipid globules are encompassed by a unit membrane known as the milk lipid globule membrane (MLGM) which is derived from the apical plasma membrane of the mammary epithelial cell during secretion. In lactating mammary epithelial cells, immediate precursors of milk lipid globules appear to be cytoplasmic lipid droplets (CLD). These cytoplasmic lipid droplets have diameters >1 μm and are characterized by an electron dense, granular surface coat. A previously unrecognized group of structures with diameters