Three fungi not previously reported on desiccated human remains were identified on cadavers at the Forensic Investigation Research Station (FIRS) in Whitewater, Colorado. The location of the FIRS provides the unique opportunity to observe the stages of decomposition in a high desert environment. The two cadavers used in the study were in the late stages of decomposition (PMI of approximately 1520 and 1820 days) to the point of desiccation and had developed an extensive black crust on How to cite this article: Becktell MC, Tucker S, Ozsoy AZ, Connor M. Identification of fungi found on desiccated human remains in an arid outdoor environment.

Bacterial infections and impaired mitochondrial DNA dynamics are associated with adverse pregnancy outcomes. Unmethylated cytosine-guanine dinucleotide (CpG) motifs are common in bacterial and mitochondrial DNA and act as potent immunostimulators. Here, we tested the hypothesis that exposure to CpG oligonucleotides (ODN) during pregnancy would disrupt blood pressure circadian rhythms and the placental molecular clock machinery, mediating aberrant fetoplacental growth dynamics. Rats were repeatedly treated with CpG ODN in the 3rd trimester (gestational day, GD, 14, 16, 18) and euthanized on GD20 (near term) or with a single dose of CpG ODN and euthanized 4 hours after treatment on GD14. Hemodynamic circadian rhythms were analyzed via Lomb-Scargle periodogram analysis on 24-h raw data collected continuously via radiotelemetry. A p-value ≥ 0.05 indicates the absence of a circadian rhythm. Following the first treatment with CpG ODN, maternal systolic and diastolic blood pressure circadian rhythms were lost (p ≥ 0.05). Blood pressure circadian rhythm was restored by GD16 and remained unaffected after the second treatment with CpG ODN (p < 0.0001). Diastolic blood pressure circadian rhythm was again lost after the last treatment on GD18 (p ≥ 0.05). CpG ODN increased placental expression of Per2 and Per3 and Tnfα (p ≤ 0.05) and affected fetoplacental growth dynamics, such as reduced fetal and placental weights were disproportionately associated with increases in the number of resorptions in ODN-treated dams compared to controls. In conclusion, gestational exposure to unmethylated CpG DNA dysregulates placental molecular clock network and fetoplacental growth dynamics and disrupts blood pressure circadian rhythms.

The coronary circulation has an innate ability to maintain constant blood flow over a wide range of perfusion pressures. This study interrogated the local metabolic hypothesis, which proposes that myocardial oxygen tension, indexed by coronary venous PO2 (CvPO2), determines the degree of coronary pressure-flow autoregulation by increasing the production of vasodilator metabolites as coronary perfusion pressure (CPP) is reduced. We tested this hypothesis by examining the extent to which dobutamine-induced increases in myocardial oxygen consumption (MVO2) under both normoxic and hypoxemic conditions, influences coronary autoregulatory capability. Experiments were performed on open-chest anesthetized swine during 20 mmHg stepwise changes in coronary perfusion pressure (CPP) from 140 to 40 mmHg, via servo-controlled roller pump. Measurements were made in 3 conditions: a) normoxia (n = 7); b) normoxia with dobutamine (10 μg/kg/min, iv; n = 7); and c) hypoxemia (PaO2 36-38 mmHg) plus dobutamine (n = 5). Under control-normoxic conditions, CvPO2 decreased from 38 ± 2 to 22 ± 1 mmHg and coronary blood flow fell from 0.93 ± 0.15 to 0.32 ± 0.03 ml/min/g as CPP was reduced from 140 to 40 mmHg. Administration of dobutamine significantly increased heart rate (~60%; P < 0.001), but the combination of hypoxemia plus dobutamine did not further influence heart rate. Further, dobutamine with and without hypoxemia significantly increased MVO2 (P < 0.001); however, CvPO2 was reduced (P < 0.001) only in the presence of hypoxemia. Calculation of closed-loop autoregulatory gain (Gc) over a CPP range of 120 to 60 mmHg (value of 1 represents perfect autoregulation) was unaffected by dobutamine alone but tended to increase when dobutamine infusion was combined with reductions in PaO2 ≤ 40 mmHg (P = 0.069). Additional analysis of the autoregulatory slope within this same CPP range revealed no differences between groups. However, there was a significant inverse association between Gc and CvPO2, measured at CPP of 100 mmHg, in the absence and presence of dobutamine-induced increases in MVO2 ± hypoxemic conditions (P < 0.001, r = -0.722). The relationship of coronary resistance (CPP range of 120 to 60 mmHg) relative to respective CvPO2 revealed that decreases in CvPO2 were not associated with changes in coronary resistance until CvPO2 fell below a relative threshold of ~ 25 mmHg (r = 0.88). These findings support the interpretation that the sensitivity of coronary autoregulatory behavior is directly coupled with the activation of local metabolic vasodilator pathways below a critical level of myocardial oxygenation. This work was supported by National Institutes of Health grant R01 HL158723. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

There are transmural differences in the structure of arteries across the left ventricular wall. For example, for arteries of the same size, wall thickness is greater in arteries of the epicardium than those from the endocardium. This observation suggests that there could be differences in their passive and active length-tension relationships, as different amounts of connective tissue or smooth muscle would be expected to alter these characteristics. We tested this hypothesis by studying similarly sized porcine coronary arteries from opposite transmural locations. Endocardial arteries had a diameter of 389 ± 33 μm (n = 8), while epicardial arteries measured 388 ± 50 μm (n = 6). A wire myograph was used to study the mechanical properties of these arteries under isometric conditions in Krebs-Henseleit buffer at 37 °C. Arteries were cut into rings with an axial length of 2 mm. Rings were repetitively stimulated to contract at increasing lengths with the addition of high extracellular K+ (80 mM). Coronary arteries developed active tension to a plateau level over approximately 3-5 min and K+-induced contractions readily washed out. Arteries from the epicardium were stiffer, as the passive-length tension curve of these vessels was elevated over arteries from the endocardium. Passive tensions at optimal length were 3.2 ± 0.4 vs. 5.6 ± 1.5 mN/mm (p < 0.05). The active tension developed in response to K+ depolarization was greater in epicardial arteries. Active tensions at optimal length were 3.4 ± 1.1 vs. 2.4 ± 0.3 mN/mm (p < 0.05). Our results represent the first comparison of transmural differences in coronary arteries under isometric tension. Our findings support the hypothesis that differences exist in the passive and active length-tension relationships of epicardial and endocardial arteries that correlate with wall thickness. R01HL158723 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Thromboxane A2 (TxA2) is a potent coronary vasoconstrictor that has been implicated in promoting decreases in myocardial perfusion in a variety of (patho)-physiologic conditions. S18886 is a promising orally-active TxA2 receptor antagonist currently approved for investigational clinical use. However, the coronary vascular effects of S18886 are unknown and its specificity and affinity for the thromboxane receptor in the coronary circulation remain unclear. We tested the hypothesis that administration of S18886 dose-dependently attenuates coronary vasoconstriction to the TxA2 mimetic U46619 without influencing coronary responses to prostaglandin F2α, acetylcholine, or smooth muscle depolarization (K+). Experiments to test this hypothesis were performed in male (n = 5) and female (n = 6) domestic swine. Hearts were excised and the left circumflex coronary artery isolated, cleaned of periadventitial fat, and cut into 3 mm rings. Isometric tension of coronary artery rings was measured in response to log order increments of U46619 (1 nM to 1 μM) with and without S18886 (0.1-100 nM). Similar isometric studies were conducted with prostaglandin F2α (10 nM-10 μM), acetylcholine (0.1-10 μM), and KCl (5-90 mM). U46619 induced concentration dependent increases in tension development of isolated coronary artery rings (average EC50 of 42 ± 19 nM). Incubation of coronary arteries with S18886 (1 nM) significantly attenuated coronary vasoconstriction to U46619 resulting in a rightward shift of the EC50 to 187 ± 38 nM (P < 0.02). Vehicle had no effect on U46619-induced contractions. Higher concentrations of S18886 (10nM and 100nM) dose-dependently reduced U46619-induced contractions by 77% ± 3 and 93% ± 6 respectively. S18886 (1 nM) antagonized coronary vasoconstriction of prostaglandin F2α (10 μM) by 68% ± 5 (P < 0.0001) but had no effect on either acetylcholine or KCl-induced contraction. Data from this investigation indicate that S18886 is an effective antagonist of U46619-induced vasoconstriction in the porcine coronary circulation. While S18886 does not influence coronary smooth muscle response to either acetylcholine or activation of L-type Ca2+ channels, attenuation of prostaglandin F2α suggests the antagonists specificity may extend beyond TxA2 receptor signaling. NIH R01HL158723 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.