PMC

A) Representative Oil red O stainings of liver sections of LDLR ^−/−/ MPO ^−/−tp and LDLR ^−/−/ MPO ^+/+tp mice fed a high-fat diet for 8 weeks, showing comparable lipid accumulation (100× magnification). B) Similar hepatic triglyceride levels in LDLR ^−/−/ MPO ^−/−tp and LDLR ^−/−/ MPO ^+/+tp mice after high-fat feeding (0.31±0.02 vs. 0.35±0.02 µg/µg protein, p = 0.24). Chow-fed LDLR ^−/−/ MPO ^+/+ mice show a lower level of liver triglycerides. C) Plasma triglyceride levels are similar in LDLR ^−/−/ MPO ^−/−tp and LDLR ^−/−/ MPO ^+/+tp animals after high-fat feeding (1.50±0.09 vs. 1.64±0.09 mmol/l, p = 0.42). D) High-fat feeding results in higher plasma cholesterol levels in LDLR ^−/−/ MPO ^+/+tp animals as compared with LDLR ^−/−/ MPO ^−/−tp mice (33.5±0.1 vs. 39.5±2.0 mmol/l, p = 0.02). E) Diet-induced liver cholesterol accumulation is reduced in LDLR ^−/−/ MPO ^−/−tp mice compared with LDLR ^−/−/ MPO ^+/+tp animals (0.072±0.004 vs. 0.090±0.004 µg/µg protein, p = 0.01), but does not reach the level observed in chow-fed LDLR ^−/−/ MPO ^+/+ mice. F) Hepatic mRNA expression of key enzymes in cholesterol metabolism is not altered in LDLR ^−/−/ MPO ^−/−tp mice, whereas scavenger receptor expression is reduced (SR-B1 1.7-fold, p<0.01; CD36 1.4-fold, p<0.01, SR-A 1.2-fold, p = 0.63).

IU vs TP, HD, and TP/HD microbiomes in the stringent data set. (A) Box plot showing Chao1 and ACE richness estimates and Shannon and Simpson diversity indices of the different ulcer groups. Significant P values: Chao1, TP vs IU, 0.043; Shannon, TP vs HD, 0.002; TP vs IU, 0.018; Simpson, TP vs HD, 0.018. (B) PCoA of microbiomes by ulcer etiology. Significant pairwise PERMANOVA P values: TP vs HD, 0.002; TP vs IU, 0.002; HD vs IU, 0.002; HD vs TP/HD, 0.002, IU vs TP/HD, 0.002. (C) Box plots of top 10 ASVs found in ulcers and comparison of their relative abundances between all ulcer etiologies. Box plots show medians with hinges corresponding to 25th and 75th percentiles and whiskers extending no further than 1.5× interquartile range from the hinges. Red diamonds signify means. Medians are shifted toward zero due to the absence of many of the ASVs in the majority of the samples. Significantly different groups and P values follow: for Treponema pallidum, IU vs TP, P < 0.001; IU vs TP/HD, P < 0.001; TP vs HD, P < 0.001; HD vs TP/HD, P < 0.001; for Streptococcus pyogenes, IU vs HD, P < 0.001; IU vs TP, P = 0.037; IU vs TP/HD, P = 0.006; HD vs TP, P = 0.008; for Haemophilus ducreyi, IU vs HD, P < 0.001; IU vs TP/HD, P < 0.001; HD vs TP, P < 0.001; HD vs TP/HD, P = 0.043; TP vs TP/HD, P < 0.001; for Staphylococcus aureus, IU vs TP, P = 0.047; IU vs TP/HD, P = 0.047; for Haemophilus ducreyi 2, HD vs TP, P = 0.014; for Haemophilus ducreyi 3, HD vs TP, P < 0.001; HD vs TP/HD, P = 0.002. Abbreviations: HD, H. ducreyi ulcers; IU, idiopathic ulcers, TP, Treponema pallidum subspecies pertenue ulcers; TP/HD, dual positive ulcers.

MCR and NNLS decomposed results of hydrate and anhydrous solid-state forms of theophylline. (a) Optical image of TP MH at 25 °C with laser line illumination (white line) from the Raman microscope (b) concentration profile of solid-state forms during isothermal dehydration at 50 °C for 90 minutes starting from TP MH to TP AH form II, via TP MS1 and TP MS2 (c1–4) chemical concentration maps (cut out artefacts from 1.8 mm laser line) of TP MH (c1), TP MS1 (c2), TP MS2 (c3), TP AH form II (c4) in the particle during dehydration where the laser line is illuminated, (d1–4) Raman spectra for TP MH, TP MS1, TP MS2 and TP AH form II respectively, (e1–e4) area plots showing only the dehydration profiles of TP metastable intermediates at four isothermal conditions (45, 50, 60 and 65 °C) where the colour under the area plots matches the TP metastable intermediates as shown in the concentration profiles. The stable forms of TP were taken into consideration for the area plots.

Generation of mice with targeted deletions of both TP and UP. (a) Levels of F₃dThd in plasma in mice after administration of F₃dThd. F₃dThd (100 mg/kg) was administered orally to TP^+/+ and TP^−/− mice. The concentration of F₃dThd in plasma was determined as described previously (). Statistical significance was determined by using the Student's t test (mean ± the standard error; n = 3). (b) TP activity in various tissues from wild-type, TP^−/−, UP^−/−, and TP^−/− UP^−/− mice. The rate of conversion of thymidine to thymine was measured radiometrically as described previously (). TP activity is expressed as nanomoles of thymidine catalyzed to thymine per minute per milligram of protein. Tissues were collected from three 2-month-old mice. (c) PCR analysis of mouse tail DNA from animals with the following six phenotypes: wild-type allele (TP^+/+ UP^+/+), heterozygous TP-null allele (TP^+/− UP^+/+), homozygous TP-null allele (TP^−/− UP^+/+), heterozygous UP-null allele (TP^+/+ UP^+/−), homozygous UP-null allele (TP^+/+UP^−/−), heterozygous TP or UP allele (TP^+/− UP^+/−), and homozygous TP- and UP-null allele (TP^−/− UP^−/−). The sizes of the amplified PCR products were 210 bp for UP wild type, 640 bp for TP wild type, 313 bp for the UP targeted allele, and 400 bp for the TP targeted allele fragments. (d) Five female mice at 5 months of age were injected intraperitoneally with pentobarbital. The time during which postural reflex was lost was measured.