658 research outputs found

    Surface-Enhanced Raman Scattering Microspectroscopy Enables the Direct Characterization of Biomineral-Associated Organic Material on Single Calcareous Microskeletons

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    Biominerals are composite materials with inorganic and organic components. The latter provide insights into how organisms control mineralization and, if derived from micro/nannofossils, into past climates. Many calcifying organisms cannot be cultured or are extinct; the only materials available for their study are therefore complex environmental samples in which the organism of interest may only be a minor component. There is currently no method for characterizing the biomineral-associated organic material from single particles within such assemblages, so its compositional diversity is unknown. Focusing on coccoliths, we demonstrate that surface-enhanced Raman scattering microspectroscopy can be used to determine the origin and composition of fossil organic matter at the single-particle level in a heterogeneous micro/nannofossil assemblage. This approach may find applications in the study of micro/nannofossil assemblages and uncultivated species, providing evolutionary insights into the macromolecular repertoire involved in biomineralization

    Effects of rumensin and bovatec on growth, feed intake, and feed efficiency in dairy calves

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    One hundred Holstein heifers were used to examine the effects of monensin (RumensinÂź) and lasalocid (BovatecÂź) included in calf starter and grower diets. Heifers were assigned alternately at birth to a starter feed containing either Rumensin (28 g/ton, 90% dry matter basis) or Bovatec (40 g/ton, 90% dry matter basis). The Bovatec group was switched to a starter feed containing 28 g Bovatec/ton (90% dry matter basis) at 6 weeks of age. Both groups were switched at 8 weeks of age to grower diets designed to deliver 100 mg/head/day of either Rumensin or Bovatec. No treatment differences were observed between birth and 8 weeks of age. Heifers were moved from individual hutches at 8 weeks of age to group pens (five heifers/pen) and remained on the same treatment for the next 84 days. During this 84-day period, heifers receiving Rumensin gained more weight at a faster rate and tended to be more efficient than heifers fed Bovatec. No differences were observed in feed intake, skeletal growth as measured by hip height, or body condition score

    Bruton's tyrosine kinase inhibition—An emerging therapeutic strategy in immune‐mediated dermatological conditions

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    Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B-cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune-mediated dermatological diseases. However, the established risk-to-benefit profile of "first-generation" BTK inhibitors cannot be extrapolated to these emerging, non-oncological, indications. "Next-generation" BTK inhibitors such as remibrutinib and fenebrutinib entered clinical development for chronic spontaneous urticaria (CSU); rilzabrutinib and tirabrutinib are being studied as potential treatments for pemphigus. Promising data from early-phase clinical trials in CSU suggest potential for these agents to achieve strong pathway inhibition, which may translate into measurable clinical benefits, as well as other effects such as the disruption of autoantibody production. BTK inhibitors may help to overcome some of the shortcomings of monoclonal antibody treatments for immune-mediated dermatological conditions such as CSU, pemphigus, and systemic lupus erythematosus. In addition, the use of BTK inhibitors may improve understanding of the pathophysiological roles of mast cells, basophils, and B cells in such conditions.info:eu-repo/semantics/publishedVersio

    In vivo non-invasive staining-free visualization of dermal mast cells in healthy, allergy and mastocytosis humans using two-photon fluorescence lifetime imaging

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    Mast cells (MCs) are multifunctional cells of the immune system and are found in skin and all major tissues of the body. They contribute to the pathology of several diseases including urticaria, psoriasis, atopic dermatitis and mastocytosis where they are increased at lesional sites. Histomorphometric analysis of skin biopsies serves as a routine method for the assessment of MC numbers and their activation status, which comes with major limitations. As of now, non-invasive techniques to study MCs in vivo are not available. Here, we describe a label-free imaging technique to visualize MCs and their activation status in the human papillary dermis in vivo. This technique uses two-photon excited fluorescence lifetime imaging (TPE-FLIM) signatures, which are different for MCs and other dermal components. TPE-FLIM allows for the visualization and quantification of dermal MCs in healthy subjects and patients with skin diseases. Moreover, TPE-FLIM can differentiate between two MC populations in the papillary dermis in vivo—resting and activated MCs with a sensitivity of 0.81 and 0.87 and a specificity of 0.85 and 0.84, respectively. Results obtained on healthy volunteers and allergy and mastocytosis patients indicate the existence of other MC subpopulations within known resting and activated MC populations. The developed method may become an important tool for non-invasive in vivo diagnostics and therapy control in dermatology and immunology, which will help to better understand pathomechanisms involving MC accumulation, activation and degranulation and to characterize the effects of therapies that target MCs
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