Miracle-dz/UniFAR-FTUs huggingface dataset:
In vivo threonine oxidation rate is dependent on threonine dietary supply in growing pigs fed low to adequate levels.

Threonine oxidation was examined in 12 growing pigs fed a well-balanced control diet or a threonine-deficient diet supplemented (Glu) or not (LT) with glutamic acid during constant infusion of L-[1-(13)C]-threonine, [1-(14)C]glycine and [1-(14)C]alpha-ketobutyrate for 10 h. During these infusion, liver glycine enrichment was significantly lower than plasma enrichment. Moreover, the pancreas to plasma glycine enrichment ratio was higher than the liver to plasma ratio (70-89%), showing that an important part of glycine de novo synthesis in pancreas occurred through the threonine dehydrogenase (TDG) pathway. These results imply that calculation of threonine oxidation into glycine should be made with the assumption of both hepatic and extrahepatic oxidation. Plateau values of plasma threonine, glycine and alpha-ketobutyrate enrichments and specific radio activities allowed estimations of threonine oxidation through the TDG and threonine dehydratase (TDH) pathways. Threonine oxidation into glycine was 12.16 +/- 2.06, 2.89 +/- 0.61 and 2.13 +/- 0.44 mumol/(kg.h), respectively, in pigs fed the control, LT and Glu diets, and threonine oxidation into alpha-ketobutyrate was 1.80 +/- 0.31, 0.88 +/- 0.02 and 0.55 +/- 0.06 mumol/ (kg.h) for the control, LT and Glu groups, respectively. Total threonine oxidation rates were 75 and 81% lower in the LT and Glu groups, respectively, than in the control group. Liver TDG and TDH activity measured in vitro were not affected by either the level of dietary threonine supply the addition of glutamic acid. On the basis of plasma data, it may be concluded that the addition of glutamic acid to a threonine-deficient diet had no significant effect on threonine oxidation but did reduce the rate of threonine release from protein breakdown. Oxidation appears to be related to plasma threonine concentration.
Extracellular matrix and pulmonary hypertension: control of vascular smooth muscle cell contractility.

Pulmonary hypertension is characterized by increased vascular resistance due to smooth muscle cell hyperactivity and excess deposition of extracellular matrix (ECM) in the vessel wall. We investigated the possibility that changes in cell-ECM interactions may play an active role in this process by modifying the contractile response of pulmonary vascular smooth muscle (PVSM) cells. Contractility was measured within individual cultured PVSM cells, when resting or stimulated with vasoactive agents, by quantitating changes in stiffness of the cytoskeleton (CSK) using magnetic twisting cytometry (N. Wang, J. P. Butler, and D. E. Ingber. Science 260: 1124-1127, 1993). Control studies confirmed that changes in CSK stiffness closely paralleled alterations in cell contraction and relaxation as measured in response to endothelin-1 (ET-1) and dibutyryl guanosine 3',5'-cyclic monophosphate (cGMP), respectively, in a collagen gel contraction assay. CSK stiffness and contractile tone in cultured PVSM cells increased in direct proportion as the density of fibronectin (FN) coating was raised from 10 to 500 ng/well in 96-well plates. Dibutyryl cGMP had no effect in cells on low FN, although it completely inhibited the FN-dependent increase in CSK stiffness on higher ECM densities. In contrast, ET-1 induced the greatest increase in CSK stiffness on the intermediate FN density (100 ng/well). The reduced sensitivity to ET-1 on high FN was not due to dysfunction of the contractile apparatus nor to changes in protein tyrosine phosphorylation. Taken together, these results show that ECM can modulate PVSM cell contractility and suggest that the changes in ECM observed in hypertensive vessels could play an important role in the etiology of this disease.
Effect of ANG II on pHi, [Ca2+]i, and contraction in rabbit ventricular myocytes from infarcted hearts.

In this study we examined Na+/H+exchange activity, Ca2+transients, and contractility in rabbit ventricular myocytes isolated from normal and chronically (8-12 wk) infarcted left ventricles. Myocytes from infarcted hearts (post-MI myocytes) were isolated from the peri-infarcted region of the left ventricle. Intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i) were measured with the fluorescent pH indicators seminaphthorhodafluor 1 and fluo 3, respectively, and contractility was assessed from changes in cell shortening during field stimulation. Experiments were performed at extracellular pH 7.4 in the presence and absence (HEPES buffer) of CO2 and[Formula: see text]. Our findings demonstrate that 1) myocytes after myocardial infarction (post-MI) were significantly larger than normal, 2) post-MI hypertrophy was not accompanied by changes in non-CO2intracellular buffering power, 3) post-MI hypertrophy did not significantly affect the ability of Na+/H+exchange to mediate pHi recovery from intracellular acidosis, 4) the stimulatory effect of ANG II (100 nM) on Na+/H+exchange was significantly reduced in post-MI myocytes, 5) in[Formula: see text]-buffered solutions, ANG II did not significantly stimulate pHirecovery from acidosis in post-MI myocytes, 6) the angiotensin AT1 receptor mediates the stimulatory action of ANG II on Na+/H+exchange in normal and post-MI myocytes, and 7) the stimulatory effect of ANG II on the Ca2+ transient and contraction was blunted in post-MI myocytes bathed in HEPES-buffered solution. A suppressed ventricular responsiveness to ANG II may be beneficial in the intact myocardium by attenuating ATP consumption and by reducing intracellular Na+accumulation during ischemia-reperfusion.
Dietary protein, carbohydrate, and fat enhance memory performance in the healthy elderly.

BACKGROUND Dietary carbohydrates can improve memory. Whether these effects are related to elevations in blood glucose or to energy ingestion is unknown. OBJECTIVES Our objectives were to determine 1) the influence of isoenergetic protein-, carbohydrate-, and fat-containing drinks on cognitive performance and 2) whether the time period after ingestion affects cognition. DESIGN After fasting overnight, 11 men and 11 women aged 61-79 y consumed either a 300-mL drink containing 774 kJ as pure protein (whey), carbohydrate (glucose), or fat (safflower oil) or a nonenergy placebo on 4 separate mornings. Cognitive tests were administered 15 and 60 min after ingestion of the drinks. Plasma glucose and serum insulin concentrations were measured. RESULTS Only the carbohydrate drink increased blood glucose (P < 0.0001). Compared with the placebo, all 3 macronutrients improved delayed paragraph recall (PR) (P < 0.001) and improved or tended to improve immediate PR (P < 0.04) 15 min after ingestion. Beneficial effects on other cognitive tests were confined to one or more of the macronutrients: carbohydrate improved Trail Making Test (Trails) performance at 60 min (P = 0.02) and tended to improve Trails at 15 min (P = 0.04) and PR at 60 min in men, carbohydrate and fat improved or tended to improve performance on Trails at 15 and 60 min in subjects with poor baseline scores (r > -0.41, P < 0.03), fat tended to improve attention at 60 min (P < 0.05), and protein reduced the rate of forgetting on the PR at 15 min (P = 0.002). CONCLUSIONS Energy intake from protein, carbohydrate, or fat can enhance memory independently of elevations in blood glucose. Each macronutrient may also exert unique effects on cognition.
De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption.

BACKGROUND Acute alcohol intake is associated with changes in plasma lipid concentrations and whole-body lipid balances in humans. The quantitative roles of hepatic de novo lipogenesis (DNL) and plasma acetate production in these changes have not been established, however. OBJECTIVE We used stable-isotope mass spectrometric methods with indirect calorimetry to establish the metabolic basis of changes in whole-body lipid balances in healthy men after consumption of 24 g alcohol. DESIGN Eight healthy subjects were studied and DNL (by mass-isotopomer distribution analysis), lipolysis (by dilution of [1,2,3,4-(13)C(4)]palmitate and [(2)H(5)]glycerol), conversion of alcohol to plasma acetate (by incorporation from [1-(13)C(1)]ethanol), and plasma acetate flux (by dilution of [1-(13)C(1)]acetate) were measured. RESULTS The fractional contribution from DNL to VLDL-triacylglycerol palmitate rose after alcohol consumption from 2 +/- 1% to 30 +/- 8%; nevertheless, the absolute rate of DNL (0.8 g/6 h) represented <5% of the ingested alcohol dose; 77 +/- 13% of the alcohol cleared from plasma was converted directly to acetate entering plasma. Acetate flux increased 2.5-fold after alcohol consumption. Adipose release of nonesterified fatty acids into plasma decreased by 53% and whole-body lipid oxidation decreased by 73%. CONCLUSIONS We conclude that the consumption of 24 g alcohol activates the hepatic DNL pathway modestly, but acetate produced in the liver and released into plasma inhibits lipolysis, alters tissue fuel selection, and represents the major quantitative fate of ingested ethanol.
Systemic arterial compliance is reduced in young patients with IDDM.

Arterial elastic properties are altered with increasing age and in various disease states, including non-insulin-dependent diabetes mellitus (NIDDM). Whether young patients with insulin-dependent diabetes mellitus (IDDM) have reduced arterial compliance before developing endothelial dysfunction or overt micro- and macrovascular disease is unclear. Systemic arterial compliance and endothelium-dependent, flow-mediated vasodilation (FMD) was assessed in 25 individuals with uncomplicated IDDM (23 ± 4 yr, 14 females and 11 males) and compared with 30 age-matched controls (15 females and 15 males). Arterial compliance was determined via simultaneous measurements of aortic blood flow and carotid arterial pressure. The relationship between arterial compliance and endothelial function (assessed by brachial artery FMD) was also examined. Arterial compliance was 29% lower in IDDM subjects compared with control subjects (0.46 ± 0.05 vs. 0.65 ± 0.07 arbitrary compliance units, P < 0.05). Blood pressure, lipid levels, and daily energy expenditure (a measure of physical activity levels) were not different between groups. Compliance in the IDDM group was not related to the integrity of endothelial vasodilator function, disease duration, or degree of glycemic control. Arterial compliance is reduced in young patients with IDDM before the development of overt micro- or macrovascular disease. Early assessment of arterial compliance may be useful in predicting the development of diabetic vascular complications.
Generation of superoxide in cardiomyocytes during ischemia before reperfusion.

Although a burst of oxidants has been well described with reperfusion, less is known about the oxidants generated by the highly reduced redox state and low O2 of ischemia. This study aimed to further identify the species and source of these oxidants. Cardiomyocytes were exposed to 1 h of simulated ischemia while oxidant generation was assessed by intracellular dihydroethidine (DHE) oxidation. Ischemia increased DHE oxidation significantly (0.7 ± 0.1 to 2.3 ± 0.3) after 1 h. Myxothiazol (mitochondrial site III inhibitor) attenuated oxidation to 1.3 ± 0.1, as did the site I inhibitors rotenone (1.0 ± 0.1), amytal (1.1 ± 0.1), and the flavoprotein oxidase inhibitor diphenyleneiodonium (0.9 ± 0.1). By contrast, the site IV inhibitor cyanide, as well as inhibitors of xanthine oxidase (allopurinol), nitric oxide synthase (nitro-l-arginine methyl ester), and NADPH oxidase (apocynin), had no effect. Finally, DHE oxidation increased with Cu- and Zn-containing superoxide dismutase (SOD) inhibition using diethyldithiocarbamate (2.7 ± 0.1) and decreased with exogenous SOD (1.1 ± 0.1). We conclude that significant superoxide generation occurs during ischemia before reperfusion from the ubisemiquinone site of the mitochondrial electron transport chain.
TREATMENT OF METAL-CONTAMINATED WATER USING BACTERIAL SULFATE REDUCTION: RESULTS FROM PILOT-SCALE REACTORS

Pilot-scale biological reactor systems were installed to treat metalcontaminated water in an underground coal mine and at a smelting residues dump in Pennsylvania. The reactors consisted of barrels and tanks filled with spent mushroom compost, within which bacterial sulfate reduction became established. Concentrations of Fe, Zn, Mn, Ni, and Cd were lowered by over 95% as these metals were precipitated in the reactors. The formation of insoluble metal sulfides by reaction with bacterially generated H2S was identified as an important metal retaining process in the reactors. This paper examines the chemistry of the reactor systems and opportunities for enhancing their metal-retaining and alkalinity-generating
IL-1β mediates leptin induction during inflammation.

Interleukins (IL) are key mediators of the host response to infection and inflammation. Leptin is secreted by adipose tissue and plays an important role in the control of food intake. Administration of lipopolysaccharide (LPS), tumor necrosis factor (TNF), or IL-1 acutely increases leptin mRNA and protein levels. To investigate the role of IL-1β and IL-6 in leptin expression during inflammation, we used IL-1β-deficient (-/-) and IL-6 -/- mice. Mice were injected intraperitoneally with LPS or subcutaneously with turpentine, as models of systemic or local inflammation, respectively. In IL-1β +/+ mice, both LPS and turpentine increased leptin mRNA and circulating leptin. In contrast, neither LPS nor turpentine increased leptin levels in IL-1β -/- mice. In IL-6 +/+ or IL-6 -/- mice, turpentine increased leptin protein to comparable levels. We conclude that IL-1β is essential for leptin induction by both LPS and turpentine in mice, but IL-6 is not.
Enzymatic Pre-Treatment Increases the Protein Bioaccessibility and Extractability in Dulse (Palmaria palmata)

Several common protein extraction protocols have been applied on seaweeds, but extraction yields have been limited. The aims of this study were to further develop and optimize existing extraction protocols and to examine the effect of enzymatic pre-treatment on bioaccessibility and extractability of seaweed proteins. Enzymatic pre-treatment of seaweed samples resulted in a three-fold increase in amino acids available for extraction. Combining enzymatic pre-treatment with alkaline extraction resulted in a 1.6-fold increase in the protein extraction yield compared to a standard alkaline extraction protocol. A simulated in vitro gastrointestinal digestion model showed that enzymatic pre-treatment of seaweed increased the amount of amino acids available for intestinal absorption 3.2-fold. In conclusion, enzymatic pre-treatment of seaweeds is effective for increasing the amount of amino acids available for utilization and may thus be an effective means for increasing the utilization potential of seaweed proteins. However, both the enzymatic pre-treatment protocol and the protein extraction protocol need further optimization in order to obtain optimal cost-benefit and results from the in vitro gastrointestinal digestion model need to be confirmed in clinical models.
In vivo imaging: shining a light on stem cells in the living animal

Stem cells are undifferentiated cells that play crucial roles during development, growth and regeneration. Traditionally, these cells have been primarily characterised by histology, cell sorting, cell culture and ex vivo methods. However, as stem cells interact in a complex environment within specific tissue niches, there has been increasing interest in examining their in vivo behaviours, particularly in response to injury. Advances in imaging technologies and genetic tools have converged to enable unprecedented access to the endogenous stem cell niche. In this Spotlight article, we highlight how in vivo imaging can probe a range of biological processes that relate to stem cell activity, behaviour and control. Summary: This Spotlight highlights how recent advances in imaging technologies have enabled stem cells to be visualised in real time within intact organ systems, revealing novel aspects of their behaviour, especially in response to injury.
Transcobalamin II synthesized in the intestinal villi facilitates transfer of cobalamin to the portal blood.

This study was designed to identify the cellular component of the intestinal villus where transcobalamin II (TCII) is synthesized, because this protein provides an essential function in the intestinal absorption of vitamin B12 (cobalamin, Cbl). When a segment of proximal or distal small intestine of the guinea pig is cultured in medium containing [57Co]Cbl, TCII-[57Co]Cbl appears within 15 min. Northern blot analysis of RNA from both proximal and distal small intestine identified the TCII transcript. In situ hybridization of the distal ileum with35S-labeled TCII antisense transcript localized grains predominantly in crypts and in the lower third and central core of the villi. Grains were also evident at the base of the enterocytes in close apposition with the vascular network, whereas few grains appeared in the apical region of the columnar cells. This study provides evidence that TCII is constitutively expressed in the intestinal villi where vascular endothelium is abundant. In the distal ileum, where the intrinsic factor (IF) receptor is expressed, after uptake of IF-Cbl and the subsequent binding of free Cbl to TCII synthesized in the villi, the TCII-Cbl complex enters the microcirculation and passes into the portal blood.
Heavy Prenatal Alcohol Exposure is Related to Smaller Corpus Callosum in Newborn MRI Scans

BACKGROUND Magnetic resonance imaging (MRI) studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure (PAE) but have not previously examined the feasibility of detecting this effect in infants. Tissue segmentation of the newborn brain is challenging because analysis techniques developed for the adult brain are not directly transferable, and segmentation for cerebral morphometry is difficult in neonates, due to the latter's incomplete myelination. This study is the first to use volumetric structural MRI to investigate PAE effects in newborns using manual tracing and to examine the cross-sectional area of the corpus callosum (CC). METHODS Forty-three nonsedated infants born to 32 Cape Coloured heavy drinkers and 11 controls recruited prospectively during pregnancy were scanned using a custom-designed birdcage coil for infants, which increases signal-to-noise ratio almost 2-fold compared to the standard head coil. Alcohol use was ascertained prospectively during pregnancy, and fetal alcohol spectrum disorders diagnosis was conducted by expert dysmorphologists. Data were acquired using a multi-echo FLASH protocol adapted for newborns, and a knowledge-based procedure was used to hand-segment the neonatal brains. RESULTS CC was disproportionately smaller in alcohol-exposed neonates than controls after controlling for intracranial volume. By contrast, CC area was unrelated to infant sex, gestational age, age at scan, or maternal smoking, marijuana, or methamphetamine use during pregnancy. CONCLUSIONS Given that midline craniofacial anomalies have been recognized as a hallmark of fetal alcohol syndrome in humans and animal models since this syndrome was first identified, the CC deficit identified here in newborns may support early identification of a range of midline structural impairments. Smaller CC during the newborn period may provide an early indicator of fetal alcohol-related cognitive deficits that have been linked to this critically important brain structure in childhood and adolescence.
Effect of nerve monitoring on complications of thyroid surgery

OBJECTIVE: The most frequent and critical complications of thyroid surgery are recurrent laryngeal nerve palsy and hypocalcemia. In first years of the 21st century, intraoperative neuromonitoring (IONM) was introduced as a new technique to avoid the recurrent laryngeal nerve (RLN) injury. However, the role and the benefits of IONM are still controversial. In this study, we aimed to compare the postoperative complication rates during thyroid surgery with IONM usage (Group 1) and conventional direct visual technique without IONM usage (Group 2). METHODS: We conducted retrospective review of all patients undergoing thyroid surgery in Lütfiye Nuri Burat State Hospital General Surgery Department between 2014 and 2016 years. Patients have been classified in to two groups: Group 1 and 2. RESULTS: Overall, 191 patients were included in the study; Group 1 comprised 79 patients and Group 2 comprised 112 patients. Unilateral RLN paralysis was observed in 7 patients in Group 1 (8.9%) and 15 patients in Group 2 (13.4%) without any significant difference between the groups (p=0.368). Hypocalcemia was encountered in 5 patients (6.3%) in Group 1 and 18 patients (16.1%) in Group 2; this difference was statistically significant (p=0.045). Other complications (such as hematoma and suture reaction) were not significantly different. Operation time was found to be significantly shorter in Group 1 (Mean time, 93.08 min) than in Group 2 (116.54 min) (p=0.03). CONCLUSION: Proven effect of IONM on RLN paralysis is still controversial. However, easy identification of RLN, which gives more confidence to surgeon, and shorter operation time may be factors to lower hypocalcemia rates.
STAT1 Promotes KRAS Colon Tumor Growth and Susceptibility to Pharmacological Inhibition of Translation Initiation Factor eIF4A

The transcription factor STAT1 displays antitumor functions for certain forms of cancer via immunoregulatory and cell-autonomous pathways. Paradoxically, STAT1 can promote the survival of different tumor types treated with chemotherapeutic drugs through mechanisms that are not clearly defined. Herein, we demonstrate that STAT1 displays prosurvival effects in human KRAS colon tumor cells by regulating pathways that converge on the initiation of mRNA translation. Specifically, STAT1 increases PI3K class IB signaling and promotes the downregulation of the programmed cell death protein 4 (PDCD4), a protein with tumor-suppressive properties. PDCD4 downregulation by STAT1 increases the activity of the translation initiation factor eIF4A, which facilitates the cap-independent translation of mRNAs encoding for the antiapoptotic XIAP and BCL-XL in colon tumors with mutated but not normal KRAS. Genetic inactivation of STAT1 impairs the tumorigenic potency of human KRAS colon tumor cells and renders them resistant to the antitumor effects of the pharmacologic inhibition of eIF4A in culture and immunodeficient mice. Our data demonstrate an important connection between mRNA translation and KRAS tumorigenesis under the control of STAT1, which can determine the susceptibility of KRAS tumors to pharmacologic inhibition of mRNA translation initiation. Mol Cancer Ther; 15(12); 3055–63. ©2016 AACR.