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Along with different life strategies, organisms have evolved dramatic cellular composition differences. Understanding the molecular basis and fitness effects of these differences is key to elucidating the fundamental characteristics of life. TOR/insulin pathways are key regulators of cell size, but whether their activity determines cell size in a systemic or tissue-specific manner awaits exploration. To that end, we measured cells in four tissues in genetically modified Drosophila melanogaster (rictorΔ2 and Mnt1) and corresponding controls. While rictorΔ2 flies lacked the Rictor protein in TOR complex 2, downregulating the functions of this element in TOR/insulin pathways, Mnt1 flies lacked the transcriptional regulator protein Mnt, weakening the suppression of downstream signalling from TOR/insulin pathways. rictorΔ2 flies had smaller epidermal (leg and wing) and ommatidial cells and Mnt1 flies had larger cells in these tissues than the controls. Females had consistently larger cells than males in the three tissue types. In contrast, dorsal longitudinal flight muscle cells (measured only in males) were not altered by mutations. We suggest that mutations in cell cycle control pathways drive the evolution of systemic changes in cell size throughout the body, but additional mechanisms shape the cellular composition of some tissues independent of these mutations.

For many decades, Duhem has been considered a paradigmatic instrumentalist, and while some commentators have argued against classifying him in this way, it still seems prevalent as an interpretation of his philosophy of science. Yet such a construal bears scant resemblance to the views presented in his own works—so little, indeed, that it might be said to constitute no more than a mere phantom with respect to his actual thought. In this article, we aim to deconstruct this phantom, tracing the sources of the misconceptions surrounding his ideas and pinpointing the sources and/or causes of its proliferation. We subsequently point out and discuss those elements of his philosophy that, taken together, support the view of him as a scientific realist of a sophisticated kind. Finally, we defend our own interpretation of his thought against suggestions to the effect that it is oriented towards neither instrumentalism nor scientific realism.

The objective of this study was to identify the relationship between metabolic syndrome (MetS) and pressure ulcers (PrU), after controlling for demographic and injury characteristics, socioeconomic factors, health behaviors and fatigue among participants with spinal cord injury (SCI). This cross-sectional study recruited 350 participants with SCI from a hospital in the western region of the USA. Blood tests and physical examination were performed. Waist circumference, high-density cholesterol, triglycerides, blood pressure and fasting glucose were used to diagnose MetS according to Criteria for Clinical Diagnosis of Metabolic Syndrome defined by the American Heart Association. All other variables were self-reported. Three-stage multivariate logistic regression models were conducted to evaluate the effects of three sequential sets of predictors, including demographic/injury, socio-environmental/behavioral and health factors, basing the order of analysis on the Theoretical Risk and Prevention Model. The prevalence of PrU and MetS was 11.0% (n=36) and 35.3% (n=115), respectively. Ethnicity, smoking, alcohol consumption and MetS were statistically associated with PrU in the full model. Participants who were non-Hispanic (odds ratio (OR)=10.30, 95% confidence interval (CI): 3.46–30.65), smokers (OR=2.69, 95% CI: 1.00–7.27) and drank over 30 drinks per month (OR=5.26, 95% CI: 1.24–22.26) had greater odds of having a PrU compared with those who were Hispanic, non-smokers and non-drinkers, respectively. We also observed a positive association between MetS and PrU (ORMetS=3.71, 95% CI: 1.45–9.52), even after controlling for all other factors. Participants who had MetS had higher odds of PrU than those without MetS after adjusting for multiple covariates. Unhealthy behaviors such as smoking and excess drinking were positively associated with PrU.

Hormonal fluctuations are known to predispose ulceration of the upper gastrointestinal tract, but to date no comparative study of their effects on the healing of pre-existing ulcers in the oral cavity and stomach has been made. We studied the effects of depletion of testosterone and of EGF on the healing of acetic acid-induced ulcers using rats having undergone bilateral orchidectomy and/or salivectomy respectively. We measured alterations in gastric acid secretion and blood flow at ulcer margins, as well as plasma levels of testosterone, gastrin and the proinflammatory cytokines IL-1 beta and TNF-alpha. Testosterone (0.01-10 mg/kg/day i. m.) dose-dependently delayed oral and gastric ulcer healing. When applied in an optimal dose of 1 mg/kg/day, this hormone significantly raised gastric acid secretion and plasma IL-1 beta and TNF-alpha levels. Attenuation of plasma testosterone levels via bilateral orchidectomy inhibited gastric acid secretion and accelerated the healing of oral and gastric ulcers, while increasing plasma gastrin levels and these effects were reversed by testosterone. Salivectomy raised plasma testosterone levels, and delayed oral and gastric ulcer healing. Treatment of salivectomised animals with testosterone further inhibited ulcer healing, and this effect was counteracted by EGF. We propose that testosterone delays ulcer healing via a fall in blood flow at the ulcer margin, a rise in plasma levels of IL-1 beta and TNF-alpha and, in the case of gastric ulcers, an increase in gastric acid secretion. EGF released from the salivary glands plays an important role in limitation of the deleterious effects of testosterone on ulcer healing.

Optically and electric-field induced linear electrooptics effect (PILEOE) was discovered during investigations of the 3-(4-Nitrophenyl)-6-N,N-diphenylamine-1-phenyl-1H-pyrazolo[3,4-b]quinoline and stilbene chromophores embedded into polymer PMMA matrices. The PILEOE was discovered in the quinoline and stilbene derivatives incorporated into the polymer PMMA matrices. one can see that the PILEOE coefficients achieve their maxima after 130–140 s of the bicolor photo-treatment with simultaneous applied electric field. For the both polarization geometries corresponding to two different electrode-laser polarizations the maximal value of the PILEOE coefficient is achieved for the two pyrazoloquinoline molecule and lower Pockels effect is achieved for the stilbene molecule. The behavior is changed drastically for cross-polarized (electrode-pump polarizations). In this case the effect is very low for pyrazoloquinoline chromophore (A and B) and is substantially larger for the C chromophore. Moreover, the absolute value of the achieved PILEOE is almost the same for co- and cross-polarized experimental geometry. The performed molecular geometry optimization and quantum chemical simulation have shown that the observed features are different for the two class of the chromophore and by different influence of external bicolor light on the photo-structural changes. For the quinoline crucial role belongs to co-planar nitrogen atoms, which are very sensitive to the geometry of photoinduced electrooptics effect. For the case of the stilbene role of the cis–trans isomerization is not so crucial and the corresponding anisotropy is almost absent contrary to the generally adopted model. For all the investigated chromophore maximal values of the PILEOE effect is smaller in the direction perpendicular the pump polarization (cross-polarized geometry) compared to the parallel (co-polarized) ones. The anisotropy is substantially larger for the quinoline chromophore compared to the stilbene ones. Analysis of photoinduced optical absorption and IR spectra of quinoline show principal role of the nitrogen-induced co-planarity inside the aromatic groups in the observed PILEOE anisotropy.

The decrease in pancreatic exocrine secretion during the course of acute pancreatitis is a well-documented process. However, the mechanisms underlying this reduced pancreatic function are not fully understood. To analyze pancreatic protein synthesis and secretion during and after cerulein-induced pancreatitis, we performed the plasma amino acid consumption test on conscious rats. After stimulation with 1 microgram cerulein/kg/h sc for 1 h, the control group with intact pancreas exhibited a decrease in plasma amino acid by about 15%, and this decrease could be abolished by the administration of the specific CCK-receptor antagonist, loxiglumide. Protein and amylase secretion were augmented by cerulein to about 400% of control values. Upon supramaximal stimulation of the pancreas with cerulein (20 micrograms/kg/h sc for 5 h), we observed a profound decrease of pancreatic secretion, which was accompanied by a more prolonged and more pronounced decrease of plasma amino acids (25%). Two hours after cessation of the supramaximal stimulation of pancreatic secretion (to induce pancreatitis), the administration of 1 microgram/kg/h of cerulein for 1 h resulted in a further decrease of amino plasma acid level, whereas no stimulation of exocrine pancreatic secretion was observed. Eighteen hours later, repeated administration of 1 microgram/kg/h of cerulein was still able to induce amino acid decrease by 20%, but again, no stimulation of exocrine pancreatic secretion was detectable. We conclude that, in the time course of acute cerulein-induced hyperstimulation, there might be an imbalance between synthesis of pancreatic enzymes (reflected by amino acid consumption) and the release of exocrine pancreatic secretion into the duodenum, which may be explained by leakage of proteolytic enzymes from damaged acinar cells into the extracellular space of the pancreas.

Hypertensive patients with left ventricular hypertrophy (LVH) have increased cardiovascular morbidity and mortality. Experimental studies indicate the importance of both the alpha and beta components of the adrenergic nervous system in the development and reversal of LVH. Therefore labetalol (L), a combined alpha and beta blocker, and propranolol (P), a nonselective beta blocker, were evaluated in a randomized, double-blind study of 35 hypertensive patients with echocardiographic evidence of LVH. Following 2 weeks of placebo, L or P was titrated as needed and tolerated to maximum total daily doses of 1600 mg and 640 mg, respectively. A thiazide diuretic was added if necessary for blood pressure control. M-mode echocardiograms were performed at baseline and after 1, 3, 6 and 12 months of blood pressure control. The echocardiograms were read independently by two blinded observers for end-diastolic dimension and wall thicknesses, and left ventricular mass. Fractional shortening, cardiac output, and peripheral vascular resistance were derived using standard formulas. Both drugs reduced blood pressure significantly and comparably. Significant changes in the echocardiographic measurements were observed as early as 1 month and usually persisted throughout the study. Both drugs decreased posterior wall thickness; however, only the decrease in propranolol group achieved statistical significance. Septal wall thickness was reduced by L at 3 and 12 months. End-diastolic dimension increased significantly in the L-treated group at 3, 6, and 12 months of therapy, whereas P had no effect on this measurement. As a consequence, the calculated left ventricular mass index was reduced by P throughout the study, but remained essentially unchanged by L until the twelfth month. Neither drug adversely affected fractional shortening. Cardiac output was significantly reduced by P, but unchanged by L, despite similar effects on heart rate by both drugs. Thus, despite their similar effects on blood pressure, L and P had different effects on cardiac morphology, which may reflect varying responses to alpha-and beta-adrenergic blockade.