Bruton’s tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fcε receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clinical studies.

Production of value-added compounds from a renewable aromatic polymer, lignin, has proven to be challenging. Chemical procedures, involving harsh reaction conditions, are costly and often result in nonselective degradation of lignin linkages. Therefore, enzymatic catalysis with selective cleavage of lignin bonds provides a sustainable option for lignin valorization. In this study, we describe the first functionally characterized fungal intracellular β-etherase from the wood-degrading white-rot basidiomycete Dichomitus squalens. This enzyme, Ds-GST1, from the glutathione-S-transferase superfamily selectively cleaved the β-O-4 aryl ether bond of a dimeric lignin model compound in a glutathione-dependent reaction. Ds-GST1 also demonstrated activity on polymeric synthetic lignin fractions, shown by a decrease in molecular weight distribution of the laccase-oxidized guaiacyl dehydrogenation polymer. In addition to a possible role of Ds-GST1 in intracellular catabolism of lignin-derived aromatic compounds, the cleavage of the most abundant linkages in lignin under mild reaction conditions makes this biocatalyst an attractive green alternative in biotechnological applications.

A new apheresis device using microprocessor control for the collection of a high-purity single-donor platelet concentrate was evaluated, as was the storage of platelets for up to 5 days in a citrate-plasticized polyvinylchloride blood bag. The study was conducted in three phases: collection of platelets for in vitro studies and determination of donor safety; autologous transfusion of platelets in healthy volunteers; and transfusion of platelets in patients requiring platelet transfusion therapy. Donors had mild hypocalcemia and minimal changes in blood counts except for a platelet count reduction from 288 +/- 50 x 10(3) (288 +/- 50 x 10(9)/L) to 217 +/- 43 x 10(3) per microL (217 +/- 43 x 10(9)/L). A mean of 3.36 +/- 1.24 x 10(11) platelets was collected in the mean volume of 214 mL with red cell and white cell contamination in the range of 10(7). Morphology and aggregation were as described previously in stored platelets. Platelet survival data in eight subjects showed a mean recovery of 61 +/- 11 percent and mean survival of 5.03 +/- 1.07 days by a weighted-mean model. Patients transfused with platelets had mean increments of 23,000 immediately and of 8000 at 24 hours; corrected count increments were 6000 at 1 hour and 4000 at 24 hours. The platelets were successful in providing hemostasis to these patients. Clinically useful 5-day-stored platelets are obtained by using this apheresis technology with a functionally closed system and a citrate-plasticized blood bag.

Obtaining correct amounts of essential elements, and avoiding toxic metals are key factors in dog health. Through analyzing major and trace elements in hair and blood of 50 healthy companion dogs using ICP-MS, we study their associations with dog characteristics and diet, hypothesizing that eating the same diet long-term results in strong correlations between hair and blood element concentrations, and that dog characteristics and diet affect element status. The correlation between hair and blood was significant for Hg (R = 0.601, p = 0.000) and Pb (R = 0.384, p = 0.010). The following associations were significant (p < 0.05): Dark hair had higher Ca and Mg compared to light hair. Females had higher hair Zn, blood Mn, and blood As compared to males. Blood Mn and Se increased, while blood Pb decreased with age. Raw diet fed dogs had higher hair Zn and Se compared to dry or mixed diet fed dogs, and lower blood Mn compared to dry diet fed dogs. Dry and mixed diet fed dogs had higher blood Cd compared to raw diet fed dogs. Mixed diet fed dogs had higher hair Ca and Mg compared to raw or dry diet fed dogs, and higher hair Pb compared to dry diet fed dogs. Wild game consumption was associated with higher blood Pb, and rice consumption with higher blood As. In conclusion, hair provides an alternative for assessing Hg and Pb exposure, and major and trace elements status is affected by hair color, sex, age, and diet.

Background To date, very few studies have compared the effects of different types of feeding practices on canine physiology, such as feeding exclusively dry, raw, or homemade foods. Objectives We aimed to report the changes in hematologic, serum biochemical, plasma folate, B 12 , and whole blood iron levels in dogs fed two different diets. Methods A pilot study was developed to compare the effects of a heat‐processed high carbohydrate (HPHC) and nonprocessed high‐fat (NPHF) diet. A total of 33 client‐owned Staffordshire Bull Terriers were used; 18 had canine atopic dermatitis, seven were healthy, and eight were grouped as “borderline” dogs since they did not fulfill at least six of Favrot's criteria. The comparisons were made between the diet groups at the end visit of the diet intervention, as well as within the diet groups during the study. Results Significant differences between and within the diet groups were observed, although the majority of outcomes remained within the RIs. The median time of diet intervention was 140 days. Red blood cell counts, mean cell hemoglobin concentrations, and platelet counts were significantly higher, and mean cell hemoglobin, mean cell volume, alkaline phosphatase, inorganic phosphorus, and cholesterol were significantly lower in the dogs fed the NPHF diet compared with those fed the HPHC diet after the diet trial was completed. In addition, folate, B 12 , and iron decreased significantly in the NPHF diet group. Conclusions This pilot study indicated that diet had an impact on blood values, although most remained within RIs, pointing out the need for further studies.