Miracle-dz/UniFAR-FTUs huggingface dataset:
Macronuclei and micronuclei in Tetrahymena thermophila contain high-mobility-group-like chromosomal proteins containing a highly conserved eleven-amino-acid putative DNA-binding sequence

HMG (high-mobility-group protein) B and HMG C are abundant nonhistone chromosomal proteins isolated from Tetrahymena thermophila macronuclei with solubilities, molecular weights, and amino acid compositions like those of vertebrate HMG proteins. Genomic clones encoding each of these proteins have been sequenced. Both are single-copy genes that encode single polyadenylated messages whose amounts are 10 to 15 times greater in growing cells than in starved, nongrowing cells. The derived amino acid sequences of HMG B and HMG C contain a highly conserved sequence, the HMG 1 box, found in vertebrate HMGs 1 and 2, and we speculate that this sequence may represent a novel, previously unrecognized DNA-binding motif in this class of chromosomal proteins. Like HMGs 1 and 2, HMGs B and C contain a high percentage of aromatic amino acids. However, the Tetrahymena HMGs are small, are associated with nucleosome core particles, and can be specifically extracted from macronuclei by elutive intercalation, properties associated with vertebrate HMGs 14 and 17, not HMGs 1 and 2. Thus, it appears that these Tetrahymena proteins have features in common with both of the major subgroups of higher eucaryotic HMG proteins. Surprisingly, a linker histone found exclusively in transcriptionally inactive micronuclei also has several HMG-like characteristics, including the ability to be specifically extracted from nuclei by elutive intercalation and the presence of the HMG 1 box. This finding suggests that at least in T. thermophila, proteins with HMG-like properties are not restricted to regions of transcriptionally active chromatin.
Ketamine decreases postoperative pain scores in patients taking opioids for chronic pain: results of a prospective, randomized, double-blind study.

BACKGROUND Patients prescribed opioids for chronic pain may suffer from inadequate postoperative pain control. Ketamine is an adjuvant demonstrating analgesic and opioid-sparing effects. We hypothesize that an intravenous ketamine infusion in addition to opioid-based patient-controlled analgesia (PCA) improves postoperative pain relief in this patient population. METHODS We evaluated 64 patients with chronic pain taking opioids undergoing nononcologic surgery. Patients were randomized to receive either postoperative hydromorphone PCA and continuous ketamine (0.2 mg/kg/hour), or hydromorphone PCA and saline. Patients provided numeric rating scale (NRS) pain scores for "worst," "average," and "least" pain following surgery. The primary outcome measure was change in patients' postoperative NRS scores compared with baseline NRS. Secondary and tertiary outcomes included postoperative day one 24-hour opioid use and the amount of opioid used 24 hours prior to hospital discharge. RESULTS Fifty-nine patients were included in the analysis. Baseline patient characteristics were similar with the exception of age. Patients using ketamine had decreased "average" pain scores (percent change between postoperative and preoperative NRS) after surgery (13.5% decrease in the ketamine group vs 15.5% increase in NRS in the placebo group, P = 0.0057). There were no differences in "worst" or "least" pain scores or postoperative opioid use. Side effects between groups were similar. CONCLUSIONS Our study demonstrates that a postoperative ketamine infusion at 0.2 mg/kg/hour in addition to opioids results in a statistically significant reduction of "average" pain scores in patients undergoing surgery who take opioids for chronic pain. However, "least" and "worst" pain scores and the amount of opioid used postoperatively did not differ between groups. Thus, the use of a postoperative ketamine infusion at 0.2 mg/kg/hour provides limited benefit in improving pain management for this challenging population.
Correlation between iron stores and QTc dispersion in chronic ambulatory peritoneal dialysis patients

Abstract Aim: We aimed to investigate the QT dispersion and corrected QT (QTc) dispersion which are suggested as the signals of ventricular arrhythmias, in patients on maintenance CAPD and to evaluate the correlation between iron stores and these electrocardiographic parameters. Materials and method: Fifty-eight patients on maintenance CAPD and 19 healthy age- and sex-matched adults without cardiac disease were included. The PD patients were divided into two groups according to whether their computerized measurements of QTc dispersion were longer than 65 ms. Results: Although QT interval was statistically significantly shorter in control group (34 ± 28 vs. 43 ± 34 ms; p < 0.05), there was no significant difference in regards to the QTc, QT dispersion and QTc dispersion between two groups. PD patients with QTc dispersion longer than 65 ms had higher levels of serum ferritin (p = 0.038) and transferrin saturation (TSAT; p = 0.022) than the others. QTc dispersion were positively correlated with ferritin (r = 0.469, p < 0.01) and TSAT (r = 0.430, p < 0.01) in CAPD patients. Conclusion: Although prolonged QTc, QT dispersion and QTc dispersion were suggested as the markers of ventricular arrhythmias we did not find any significant difference in regards to these parameters between control patients and CAPD patients. But the high body iron stores in these patients increase the risk of increased QT dispersion. The concern over iron overload in dialysis patients is not only because of its oxidative toxicity, but also its precipitation of arrhythmias, which may be measured by the surrogate marker of QTc dispersion.
Meteoric smoke fallout revealed by superparamagnetism in Greenland ice

Meteoric material reaching Earth contains an appreciable percentage of iron, much of which can be oxidized into nanometric‐size particles produced by ablation and subsequent condensation in the atmosphere. New measurements of isothermal remanent magnetization (IRM) show that magnetic particles of extraterrestrial origin can be distinguished from terrigenous particles based on their smaller superparamagnetic (SP) size as inferred from magnetic relaxation and by the poor correlation of the SP fraction with dust contents. The magnetic relaxation data suggest that extraterrestrial magnetic particles are in the size range of about 7–17 nm, which is compatible with the expected size of condensed particles. The concentration of extraterrestrial material in Greenland ice was estimated from the magnetic relaxation data. Assuming an iron content typical of average chondritic composition, the results correspond to a particles concentration of 0.78 ± 0.22 ppb for Greenland, good agreement with results based on iridium concentrations in NGRIP ice samples.
Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose.

The hypolipidemic effects of pantothenic acid derivatives (phosphopantothenate, panthenol and pantethine) were studied in mice with hypothalamic obesity. Hypothalamic obesity in mice was induced by single injection of aurothioglucose (300 mg/kg body wt, i.p.). All the tested substances were administered during the last 10 days before decapitation (i.m., of dosage equivalent to 150 mg/kg body wt of phosphopantothenate). The studied substances inhibited the weight gain of the animals with hypothalamic obesity over the last 10 days of the experiment. The treatment with aurothioglucose increased food intake and mean body weight, blood glucose level; insulin, serum total cholesterol, triglyceride, the sum of LDL + VLDL and LDL-cholesterol concentration; triglyceride and cholesterol fractions in the liver; triglyceride and FFA content as well as lipoprotein lipase activity in adipose tissue of experimental mice. The administration of the assay compounds lowered food intake and mean body weight, insulin and glucose levels and decreased the content of triglycerides, total cholesterol and cholesterol esters in serum and adipose tissue as well as raised the activity of lipoprotein lipase in adipose tissue and serum lipolytic activity in obese mice. Among the compounds studied the reverse effect of panthenol was especially pronounced. The mechanism of hypolipidemic effects of pantothenic acid derivatives can be related to the reduced resistance to insulin and activation of lipolysis in serum and adipose tissue.
Persistent effect of treatment with candesartan cilexetil on blood pressure in spontaneously hypertensive rats

We have investigated whether the angiotensin II type-1 (AT1) receptor antagonist, candesartan cilexetil, has a persistent effect on blood pressure even after withdrawal of treatment, as has been shown consistently for angiotensin-converting enzyme inhibitors (ACE-1). Spontaneously hypertensive rats (SHR) were divided into four groups (n=16 per group) and treated with candesartan cilexetil (high-dose: 5 mg/kg/day; middle-dose: 1 mg/kg/day; low-dose: 0.5 mg/kg/day) or control from age four weeks to 20 weeks. Normotensive Wistar-Kyoto rats (WKY) were also investigated. The drug was given in the drinking water, the concentration adjusted for water consumption and rat weight. Blood pressure (BP) was measured regularly by the indirect tail-cuff method during the treatment period and after treatment, from age 20 weeks to 32 weeks. At age 20 weeks, candesartan treatment had caused a slight reduction in body weight, an increase in water consumption and a reduction in heart rate. During treatment, candesartan caused a dose-dependent reduction in BP. After withdrawal of treatment, BP increased but remained lower than that of untreated control SHR for the medium- and high-dose groups throughout the follow-up period, the reduction being 8—11% at the end of follow-up. At age 32 weeks, there was no significant difference between the three candesartan-treated groups. We conclude that treatment with the AT1-receptor antagonist candesartan has a modest persistent effect on BP after withdrawal of treatment.
Cognitive, Perceptual, and Personal-Social Development of Prematurely Born Preschoolers

This study was designed to determine possible differences in the cognitive, perceptual, and personal-social development of prematurely and maturely born 3-yr. -olds which might foreshadow later learning problems. The subjects were 40 prematurely born graduates of a neonatal intensive care unit (birth weight < 2,500 gm, < 37 wk. gestation) matched on the pair-level with full-term controls on sex, race, post-conceptual age, and socioeconomic background. All subjects were singletons and parity was matched at the group level. No differences were found between the groups on tests of higher mental processes including the General Cognitive, Verbal, Quantitative, and Memory Scales of the McCarthy Scales of Children's Abilities, and researcher-devised measures of problem-solving competence. No differences in parental reports of personal-social development were noted. Prematures did not perform as well as controls on perceptual performance tasks, and this difference was interpreted as reflecting relatively impaired visual-motor coordination.
Protective Effect of Isoliquiritigenin against Ethanol-Induced Hepatic Steatosis by Regulating the SIRT1-AMPK Pathway

Ethanol-induced fat accumulation, the earliest and most common response of the liver to ethanol exposure, may be involved in the pathogenesis of liver diseases. Isoliquiritigenin (ISL), an important constituent of Glycyrrhizae Radix, is a chalcone derivative that exhibits antioxidant, anti-inflammatory, and phytoestrogenic activities. However, the effect of ISL treatment on lipid accumulation in hepatocytes and alcoholic hepatitis remains unclear. Therefore, we evaluated the effect and underlying mechanism of ISL on ethanol-induced hepatic steatosis by treating AML-12 cells with 200 mM ethanol and/or ISL (0∼50 μM) for 72 hr. Lipid accumulation was assayed by oil red O staining, and the expression of sirtuin1 (SIRT1), sterol regulatory element-binding protein-1c (SREBP-1c), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor alpha (PPARα) was studied by western blotting. Our results indicated that ISL treatment upregulated SIRT1 expression and downregulated SREBP-1c expression in ethanol-treated cells. Similarly, oil red O staining revealed a decrease in ethanolinduced fat accumulation upon co-treatment of ethanol-treated cells with 10, 20, and 50 μM of ISL. These findings suggest that ISL can reduce ethanol induced-hepatic lipogenesis by activating the SIRT1-AMPK pathway and thus improve lipid metabolism in alcoholic fatty livers.
Public opinion and american foreign policy

A simple and powerful new paraxial ray formalism is shown to provide an alternate method for designing Gaussian Beam Resonators. The theory utilizes the Delano or yybar diagram approach and is an extension of the recent work by Shack and Kessler for laser systems. The method is shown to be complementary to the conventional ABCD method and is founded upon J.A. Arnaud's pioneering ideas for complex rays. The thesis develops an analytic formulation of a ray based complex wavefront curvature and yields a clearly generalized description of spherical wave propagation, for which Gaussian beams are considered a special case. The resultant theory unifies the complex q parameter and the ABCD law, with the yybar complex ray components and also suggests that the ABCD law for the complex q parameter has its origin in the yybar complex ray. New fundamental equations for designing stable multi -element resonators using the yybar coordinates are derived, and it is shown that the yybar diagram provides a novel method for defining automatically stable resonators. Various applications for the yybar design technique are also discussed, including the setting of convenient design constraints, the description of M beams, generating phase diagrams, and resonator synthesis and analysis.
Natural Porcine Surfactant (Curosurf®) Down-Regulates mRNA of Tumor Necrosis Factor-α (TNF-α) and TNF-α Type II Receptor in Lipopolysaccharide-Stimulated Monocytes

We have previously shown that Curosurf®, a natural porcine surfactant, and its phospholipids effectively suppressed secretion of tumor necrosis factor (TNF-α) by resting and through lipopolysaccharide(LPS)-stimulated human monocytes. In this study the effect of Curosurf® on monocyte mRNA for TNF-α and TNF-α type II-receptor(TNF-α-RII) were analyzed to evaluate the cellular mechanisms involved in the modulation of TNF-α expression. LPS-stimulated monocytes simultaneously exposed to Curosurf® (500 µg/mL for 24 h) expressed approximately 70% less TNF-α mRNA when compared with control subjects(p < 0.05). In addition, 86% less TNF-α RII mRNA was found in monocytes exposed to Curosurf® (p < 0.001). Decreased mRNA expression was clearly associated with significantly reduced secretion of TNF-α protein (Curosurf®-exposed LPS-stimulated monocytes 3628 ± 1873 pg/mL TNF, LPS-stimulated monocytes 31 376± 2524 pg/mL TNF; mean ± SEM, p < 0.001). The activation of the transcription factor nuclear factor-κB upon LPS stimulation is not affected by Curosurf® incubation. This excludes that the decrease in mRNA and protein levels of TNF-α and TNF-α-RII is due to an inhibition of nuclear factor-κB activation by Curosurf®. We conclude that Curosurf® affects TNF-α release of LPS-stimulated monocytes at a pretranslational site by down-regulating both mRNA for TNF-α and TNF-α-RII, therefore acting as an anti-inflammatory agent within alveolar space.
Rainfall intensification in tropical semi-arid regions: the Sahelian case

An anticipated consequence of ongoing global warming is the intensification of the rainfall regimes meaning longer dry spells and heavier precipitation when it rains, with potentially high hydrological and socio-economic impacts. The semi-arid regions of the intertropical band, such as the Sahel, are facing particularly serious challenges in this respect since their population is strongly vulnerable to extreme climatic events. Detecting long term trends in the Sahelian rainfall regime is thus of great societal importance, while being scientifically challenging because datasets allowing for such detection studies are rare in this region. This study addresses this challenge by making use of a large set of daily rain gauge data covering the Sahel (defined in this study as extending from 20°W–10°E and from 11°N–18°N) since 1950, combined with an unparalleled 5 minute rainfall observations available since 1990 over the AMMA-CATCH Niger observatory. The analysis of the daily data leads to the assertion that a hydro-climatic intensification is actually taking place in the Sahel, with an increasing mean intensity of rainy days associated with a higher frequency of heavy rainfall. This leads in turn to highlight that the return to wetter annual rainfall conditions since the beginning of the 2000s—succeeding the 1970–2000 drought—is by no mean a recovery towards the much smoother regime that prevailed during the 1950s and 1960s. It also provides a vision of the contrasts existing between the West Sahel and the East Sahel, the East Sahel experiencing a stronger increase of extreme rainfall. This regional vision is complemented by a local study at sub-daily timescales carried out thanks to the 5 minute rainfall series of the AMMA-CATCH Niger observatory (12000 km2). The increasing intensity of extreme rainfall is also visible at sub-daily timescales, the annual maximum intensities have increased at an average rate of 2%–6% per decade since 1990 for timescales ranging from 5 min to 1 hour. Both visions—regional/long term/daily on the one hand, and local/27/years/sub-daily, on the other—converge to the conclusion that, rather than a rainfall recovery, the Sahel is experiencing a new era of climate extremes that roughly started at the beginning of this century.
The UL36 Tegument Protein of Herpes Simplex Virus 1 Has a Composite Binding Site at the Capsid Vertices

ABSTRACT Herpesviruses have an icosahedral nucleocapsid surrounded by an amorphous tegument and a lipoprotein envelope. The tegument comprises at least 20 proteins destined for delivery into the host cell. As the tegument does not have a regular structure, the question arises of how its proteins are recruited. The herpes simplex virus 1 (HSV-1) tegument is known to contact the capsid at its vertices, and two proteins, UL36 and UL37, have been identified as candidates for this interaction. We show that the interaction is mediated exclusively by UL36. HSV-1 nucleocapsids extracted from virions shed their UL37 upon incubation at 37°C. Cryo-electron microscopy (cryo-EM) analysis of capsids with and without UL37 reveals the same penton-capping density in both cases. As no other tegument proteins are retained in significant amounts, it follows that this density feature (∼100 kDa) represents the ordered portion of UL36 (336 kDa). It binds between neighboring UL19 protrusions and to an adjacent UL17 molecule. These observations support the hypothesis that UL36 plays a major role in the tegumentation of the virion, providing a flexible scaffold to which other tegument proteins, including UL37, bind. They also indicate how sequential conformational changes in the maturing nucleocapsid control the ordered binding, first of UL25/UL17 and then of UL36.
SORTING NEXIN1 Is Required for Modulating the Trafficking and Stability of the Arabidopsis IRON-REGULATED TRANSPORTER1[W]

This work shows that the Arabidopsis SORTING NEXIN family proteins are required to recycle the metal transporter IRT1 from the endosomal compartments back to the plasma membrane of root epidermis cells, ensuring efficient iron acquisition. Dicotyledonous plants growing under limited iron availability initiate a response resulting in the solubilization, reduction, and uptake of soil iron. The protein factors responsible for these steps are transmembrane proteins, suggesting that the intracellular trafficking machinery may be involved in iron acquisition. In search for components involved in the regulation of Arabidopsis thaliana iron deficiency responses, we identified the members of the SORTING NEXIN (SNX) protein family. SNX loss-of-function plants display enhanced susceptibility to iron deficiency in comparison to the wild type. The absence of SNX led to reduced iron import efficiency into the root. SNX1 showed partial colocalization with the principal root iron importer IRON-REGULATED TRANSPORTER1 (IRT1). In SNX loss-of-function plants, IRT1 protein levels were decreased compared with the wild type due to enhanced IRT1 degradation. This resulted in diminished amounts of the IRT1 protein at the plasma membrane. snx mutants exhibited enhanced iron deficiency responses compared with the wild type, presumably due to the lower iron uptake through IRT1. Our results reveal a role of SNX1 for the correct trafficking of IRT1 and, thus, for modulating the activity of the iron uptake machinery.
A dry ligand-binding cavity in a solvated protein

Ligands usually bind to proteins by displacing water from the binding site. The affinity and kinetics of binding therefore depend on the hydration characteristics of the site. Here, we show that the extreme case of a completely dehydrated free binding site is realized for the large nonpolar binding cavity in bovine β-lactoglobulin. Because spatially delocalized water molecules may escape detection by x-ray diffraction, we use water 17O and 2H magnetic relaxation dispersion (MRD), 13C NMR spectroscopy, molecular dynamics simulations, and free energy calculations to establish the absence of water from the binding cavity. Whereas carbon nanotubes of the same diameter are filled by a hydrogen-bonded water chain, the MRD data show that the binding pore in the apo protein is either empty or contains water molecules with subnanosecond residence times. However, the latter possibility is ruled out by the computed hydration free energies, so we conclude that the 315 Å3 binding pore is completely empty. The apo protein is thus poised for efficient binding of fatty acids and other nonpolar ligands. The qualitatively different hydration of the β-lactoglobulin pore and carbon nanotubes is caused by subtle differences in water–wall interactions and water entropy.