Melanism as a potential thermal benefit in eastern fox squirrels (Sciurus niger)

Melanistic fox squirrels (Sciurus niger) have expanded westward and increased in frequency in the Omaha, Nebraska, and Council Bluffs, Iowa, metropolitan areas. The selective advantage of melanism is currently unknown, but thermal advantages have been hypothesized, especially in winter. No difference in metabolic response curves were measured between melanistic (black) and rufus (orange) fox squirrels. When exposed to sunny skies, both melanistic and rufus squirrels had higher surface (skin and fur) temperature as ambient temperatures increased. Melanistic squirrel surface temperatures did not differ when squirrels were exposed to sunny or cloudy skies. However, rufus individuals showed significantly lower increases in surface temperatures when under cloudy skies. During fall months, rufus individuals were about 1.5 times more active throughout the day than melanistic individuals. However, in winter, melanistic fox squirrels were approximately 30% more active in the mornings (before 13:00) compared to rufus squirrels. Pre-winter body condition was higher in melanistic (25.5 ± 1.8 g/cm) compared to rufus (20.30 ± 3.6 g/cm) fox squirrels; however, there were no significant differences between melanistic (22.8 ± 1.4 g/cm) and rufus (23.9 ± 0.8 g/cm) fox squirrel post-winter body condition. The results of this study indicate that melanistic fox squirrels may have a slight winter thermal advantage over rufus fox squirrels by maintaining higher skin temperatures

Dependence of copolymer sequencing based on lactone ring size and ε-substitution

The copolymerization of an ε-substituted ε-lactone, menthide (MI), and a range of nonsubstituted lactones (6-, 7-, 8-, and 9-membered rings) was investigated in order to determine the factors that affect the sequencing of the MI copolymers. Analysis by quantitative 13C NMR spectroscopy showed the copolymerization of MI with a nonsubstituted lactone of ring size 7 or less produced a randomly sequenced copolymer, as a consequence of the smaller lactone polymerizing first and undergoing rapid transesterification as MI was incorporated. Conversely, copolymerization with larger ring lactones (ring size 8 and above) produced block-like copolymers as a consequence of MI polymerizing initially, which does not undergo rapid transesterification side reactions during the incorporation of the second monomer. Terpolymerizations of a small ring lactone, macrolactone, and menthide demonstrated methods of producing lactone terpolymers with different final sequences, depending on when the small ring lactone was injected into the reaction mixture

Nineteenth-Century Popular Science Magazines, Narrative, and the Problem of Historical Materiality

In his Some Reminiscences of a Lecturer, Andrew Wilson emphasizes the importance of narrative to popular science lecturing. Although Wilson promotes the teaching of science as useful knowledge in its own right, he also recognizes that the way science is taught can encourage audiences to take the subject up and read further on their own. Form, according to Wilson, should not be divorced from scientific content and lecturers should ensure that not only is their science accurate, but that it is presented in a way that will provoke curiosity and stimulate interest. This paper discusses the influence of narrative in structuring scientific objects and phenomena, and considers the consequences of such presentations for historical research. As scientific journalism necessarily weaves both its intended audience and the objects under discussion into its accounts, these texts demand that we recognize their nature as social relationships inscribed in historical objects

Furan Functionalized Polyesters and Polyurethanes for Thermally Reversible Reactive Hotmelt Adhesives

New reactive hotmelt (RHM) adhesives based on thermally reversible Diels-Alder networks comprising multifunctional furan and maleimide prepolymers are described. The prepolymer mixture is easy to apply in the bulk from the melt and after application to the substrates, the adhesive undergoes polymerization at room temperature resulting in crosslinked bonds. Due to their thermoplastic nature and low melt viscosity at hot melt application temperatures, the adhesives provide processing properties similar to moisture cured polyurethanes (PUR). The technology is isocyanate-free and does not require moisture to initiate the crosslinking. Bonding and tensile properties of the RHM adhesive can be readily tuned by prepolymer design and provide cure rates similar to PUR adhesives. The Diels-Alder adhesives provide versatile adhesion to a variety of substrates and good creep resistance up to the retro temperature. The adhesives show good thermal stability during application and can be recycled multiple times by simple heating/cooling of the bonds providing similar performance. Several furan and maleimide prepolymers were scaled up to multi-Kg quantities to demonstrate the potential for industrial scalability. The results demonstrate that furan-maleimide reversible chemistry can be used for RHM application as a more sustainable alternative to conventional moisture curing PURs which tend to contain harmful residual isocyanate monomers

Gilteritinib monotherapy as a transplant bridging option for high risk FLT3-mutated AML with t(6;9)(p23;q34.1);DEK-NUP214 in morphological but not cytogenetic or molecular remission following standard induction chemotherapy

We report a case of FLT3-mutated AML with t(6;9) in which induction chemotherapy with DA and midostaurin failed to achieve complete cytogenetic or molecular remission. Due to the COVID-19 pandemic and co-existing cellulitis, monotherapy with the selective FLT3-inhibitor gilteritinib was used as an alternative consolidation treatment option rather than further intensive chemotherapy. Gilteritinib was able to achieve complete molecular and cytogenetic remission despite the additional cytogenetic abnormality. This case provides supporting evidence for the use of single agent gilteritinib in high-risk primary refractory FLT3-mutated AML with t(6;9) prior to transplantation

The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer

Protein ubiquitination is a critical regulator of cellular homeostasis. Aberrations in the addition or removal of ubiquitin can result in the development of cancer and key components of the ubiquitination machinery serve as oncogenes or tumour suppressors. An emerging target in the development of cancer therapeutics are the deubiquitinase (DUB) enzymes that remove ubiquitin from protein substrates. Whether this class of enzyme plays a role in cervical cancer has not been fully explored. By interrogating the cervical cancer data from the TCGA consortium, we noted that the DUB USP13 is amplified in ~15% of cervical cancer cases. We confirmed that USP13 expression was increased in cervical cancer cell lines, cytology samples from patients with cervical disease and in cervical cancer tissue. Depletion of USP13 inhibited cervical cancer cell proliferation. Mechanistically, USP13 bound to, deubiquitinated and stabilised Mcl-1, a pivotal member of the anti-apoptotic BCL-2 family. Furthermore, reduced Mcl-1 expression partially contributed to the observed proliferative defect in USP13 depleted cells. Importantly, the expression of USP13 and Mcl-1 proteins correlated in cervical cancer tissue. Finally, we demonstrated that depletion of USP13 expression or inhibition of USP13 enzymatic activity increased the sensitivity of cervical cancer cells to the BH3 mimetic inhibitor ABT-263. Together, our data demonstrates that USP13 is a potential oncogene in cervical cancer that functions to stabilise the pro-survival protein Mcl-1, offering a potential therapeutic target for these cancers

Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria

Metabolomic analyses in alkaptonuria (AKU) have recently revealed alternative pathways in phenylalanine-tyrosine (phe-tyr) metabolism from biotransformation of homogentisic acid (HGA), the active molecule in this disease. The aim of this research was to study the phe-tyr metabolic pathway and whether the metabolites upstream of HGA, increased in nitisinone-treated patients, also undergo phase 1 and 2 biotransformation reactions. Metabolomic analyses were performed on serum and urine from patients partaking in the SONIA 2 phase 3 international randomised-controlled trial of nitisinone in AKU (EudraCT no. 2013-001633-41). Serum and urine samples were taken from the same patients at baseline (pre-nitisinone) then at 24 and 48 months on nitisinone treatment (patients N = 47 serum; 53 urine) or no treatment (patients N = 45 serum; 50 urine). Targeted feature extraction was performed to specifically mine data for the entire complement of theoretically predicted phase 1 and 2 biotransformation products derived from phenylalanine, tyrosine, 4-hydroxyphenylpyruvic acid and 4-hydroxyphenyllactic acid, in addition to phenylalanine-derived metabolites with known increases in phenylketonuria. In total, we observed 13 phase 1 and 2 biotransformation products from phenylalanine through to HGA. Each of these products were observed in urine and two were detected in serum. The derivatives of the metabolites upstream of HGA were markedly increased in urine of nitisinone-treated patients (fold change 1.2–16.2) and increases in 12 of these compounds were directly proportional to the degree of nitisinone-induced hypertyrosinaemia (correlation coefficient with serum tyrosine = 0.2–0.7). Increases in the urinary phenylalanine metabolites were also observed across consecutive visits in the treated group. Nitisinone treatment results in marked increases in a wider network of phe-tyr metabolites than shown before. This network comprises alternative biotransformation products from the major metabolites of this pathway, produced by reactions including hydration (phase 1) and bioconjugation (phase 2) of acetyl, methyl, acetylcysteine, glucuronide, glycine and sulfate groups. We propose that these alternative routes of phe-tyr metabolism, predominantly in urine, minimise tyrosinaemia as well as phenylalanaemia

Acute Exposure to Artesunate and its Effect on the Hematological Indices, Hepatotoxicity and Histology of the Liver of Adult Wistar Rats

Abstract: The effect of artesunate on the hematological indices, hepatotoxicity and histology of liver was investigated in 20 adult male wistar rats. The animals were divided into 4 groups of 5 each and group 1 which served as control were administered normal saline while groups 2, 3 and 4 were administered 1, 2 and 5 mg/kg/day respectively for a period of 5 days. The animals were humanely sacrificed on the sixth day and blood samples were obtained for hematological indices and serum enzyme analysis. The liver were excised and processed for light microscopy using the H & E stain. Hematological indices indicated insignificant difference in the RBC, WBC and DC counts, while a significant dose dependent increase in PCV and hemoglobin were observed (p<0.05). No changes were observed in the serum levels of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) among the groups. Histological examination of the liver revealed points of focal necrosis among the treated groups. The mild liver tissue damage was more evident among the over dosed group. Artesunate is thus safe, when administered within the therapeutic range