Miracle-dz/UniFAR-FTUs huggingface dataset:
The Or gene enhances carotenoid accumulation and stability during post-harvest storage of potato tubers.

Provitamin A carotenoids in staple crops are not very stable during storage and their loss compromises nutritional quality. To elucidate the fundamental mechanisms underlying carotenoid accumulation and stability, we investigated transgenic potato tubers that expressed the cauliflower Orange (Or) gene. We found that the Or transgene not only promoted retention of β-carotene level, but also continuously stimulated its accumulation during 5 months of cold storage. In contrast, no increased levels of carotenoids were observed in the tubers of vector-only controls or a yellow-flesh variety during the same period of storage. The increased carotenoid accumulation was found to be associated with the formation of lipoprotein-carotenoid sequestering structures, as well as with the enhanced abundance of phytoene synthase, a key enzyme in the carotenoid biosynthetic pathway. Furthermore, the provitamin A carotenoids stored were shown to be stable during simulated digestion and accessible for uptake by human intestinal absorptive cells. Proteomic analysis identified three major functional groups of proteins (i.e. heat shock proteins, glutathione-S-transferases, and carbohydrate metabolic proteins) that are potentially important in the Or-regulated carotenoid accumulation. Our results show that regulation of carotenoid sequestration capacity is an important mechanism by which carotenoid stability is regulated. Our findings suggest that induction of a proper sink structure formation in staple crops may provide the crops with a unique ability to promote and/or stabilize provitamin A accumulation during plant growth and post-harvest storage.
Evaluation of the Asymptomatic Athlete With Hepatic and Urinalysis Abnormalities

In general, there is no reason to evaluate either liver function tests or a urinalysis in asymptomatic athletes. However, at times they are ordered inadvertently, and when abnormal, the provider faces a quandary - ignore or evaluate them. Up to 20% of the liver function tests and urinalyses can be abnormal in the asymptomatic healthy athlete. The key concept for the provider is to quickly, accurately, and economically identify results that are normal variants from those that may be a prelude to a pathologic process. This article will discuss the most common etiologies of these abnormal laboratory tests as well as provide a framework to the follow-up evaluation. Our goal is to aid clinicians in keeping their athletes participating in their sports while at the same time not missing any significant illnesses.
Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy

Muscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal and atrophying muscles and found a unique gene fragment that is induced more than ninefold in muscles of fasted mice. We cloned this gene, which is expressed specifically in striated muscles. Because this mRNA also markedly increases in muscles atrophying because of diabetes, cancer, and renal failure, we named it atrogin-1. It contains a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, the other components of SCF-type Ub-protein ligases (E3s), as well as a nuclear localization sequence and PDZ-binding domain. On fasting, atrogin-1 mRNA levels increase specifically in skeletal muscle and before atrophy occurs. Atrogin-1 is one of the few examples of an F-box protein or Ub-protein ligase (E3) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy in diverse diseases.
Proton Pump Activation in Stimulated Parietal Cells Is Regulated by Gastric Acid Secretory Capacity: A Human Study

Under normal physiological conditions, gastric acid production is controlled by a negative feedback mechanism. Proton pump inhibitors, such as pantoprazole, inhibit gastric acid secretion by irreversibly binding and inactivating luminally active hydrogen potassium ATPase. Recovery of acid production after treatment with a proton pump inhibitor is driven by new pump synthesis, activation of existing cytoplasmic pumps, or reversal of proton pump inhibition. The authors measured the time course of the inhibition and recovery of acid secretion in healthy volunteers following intravenous administration of pantoprazole to determine the rate of proton pump activation under maximally stimulated conditions. Gastric acid production was measured in 27 Helicobacter pylori negative healthy volunteers (mean age = 31 ± 7 years; 17 men, 10 women) who received single doses of intravenous pantoprazole (20, 40, 80, or 120 mg) in the presence of a continuous intravenous infusion of 1 ug/kg/h of pentagastrin. From the time profile of acid secretion, the authors described the rate of change of acid output using an irreversible pharmacodynamic response model represented by the equation dR/dt = −k ṁ R ṁ Cpanto + Ln2/PPR ṁ (Ro‐R) and correlated the parameter values with demographic factors and gastric acid measurements. Mean stimulated acid output secretion was 21.6 ± 18.4 mEq/h (range: 1.6–90.5) prior to the administration of pantoprazole and remained steady for 25 hours after placebo administration. Intravenous pantoprazole inhibited acid output in a dose‐response fashion, with maximal inhibition (99.9%) occurring after an 80 mg dose. Mean proton pump recovery time was 37.1 ± 21.0 hours (range: 6.7–75), and recovery was independent of the dose of pantoprazole. There was no association noted between proton pump recovery time and gender, age, race, body weight, or pantoprazole dose. However, there was an inverse correlation between acid output during baseline stimulation and recovery of acid secretion. Mean proton pump recovery time in stimulated normal human volunteers was 37.1 ± 21.0 hours, with a range of 6.7 to 75 hours. The authors hypothesize that there may be a normal homeostatic mechanism that maintains acid secretory capability within a normal range by altering the rate of proton pump activation dependent on the individual's parietal cell mass. Abnormalities of this process may be responsible for the development of acid peptic disease in susceptible individuals.
CatBoost: gradient boosting with categorical features support

In this paper we present CatBoost, a new open-sourced gradient boosting library that successfully handles categorical features and outperforms existing publicly available implementations of gradient boosting in terms of quality on a set of popular publicly available datasets. The library has a GPU implementation of learning algorithm and a CPU implementation of scoring algorithm, which are significantly faster than other gradient boosting libraries on ensembles of similar sizes.
Personal characteristics relating to risk of invasive epithelial ovarian cancer in older women in the United States

Background. The ovarian cancer incidence rate is higher for women over 55 years of age than for younger women, but it increases less rapidly with age after age 55 years than before. This slower rate of increase suggests that the postmenopausal ovary may be less exposed or less susceptible than the functioning one to endogenous or exogenous carcinogens. For example, it is not exposed to mitotic stimuli at follicle rupture, which may increase the likelihood of malignancy.
Down‐regulation of pili and capsule of Neisseria meningitidis upon contact with epithelial cells is mediated by CrgA regulatory protein

The initial attachment of Neisseria meningitidis to the target cell surface appears to be largely pilus depend‐ent in capsulated bacteria. Intimate adhesion subsequently occurs to permit colonization. We recently reported that insertional inactivation of the crgA gene, which encodes a transcriptional regulator belonging to the LysR family, decreased meningococcal adhesion to epithelial cells and abolished intimate adhesion. In this report, we analyse expression of the pilE and sia genes, which are involved in the biosynthesis of pili and capsule respectively, during bacteria–host cell interactions. Western blotting, transcriptional fusion and reverse transcriptase polymerase chain reaction (RT‐PCR) analysis showed that the expression of these genes was downregulated during intimate adhesion. DNA‐binding assays, footprinting and RT‐PCR analysis indicated that this downregulation was directly mediated by the CrgA protein. The pilE and sia promoters were found to have a CrgA binding motif in common. These results strongly suggest that N. meningitidis displays an adaptive response upon cell contact. CrgA may play a central regulatory role in meningococcal adhesion, particularly in switching from initial to intimate adhesion by downregulating the bacterial surface structures that hinder this adhesion.
HER2/neu (c‐erbB‐2) gene amplification and protein expression are rare in uterine cervical neoplasia: a tissue microarray study of 814 archival specimens

Published studies have reported widely variable incidence of HER2/neu (c‐erbB‐2) protein expression and HER2/neu (c‐erbB‐2) gene amplification in cervical carcinoma. We examined tissue microarrays (TMAs) constructed from 814 formaldehyde‐fixed paraffin‐embedded archival specimens of cervical intraepithelial neoplasia (CIN)1 (n = 262), CIN2 (n = 230), CIN3 (n = 186) and invasive carcinoma (n = 136), for HER2/neu protein expression by immunohistochemistry (IHC) and for HER2/neu gene amplification by chromogenic in situ hybridization (CISH). We found moderate or strong immunohistochemical positivity for HER2/neu in 64 of 814 specimens (7.9%). Using CISH, polysomy of the HER2/neu gene was detected in 87 cases (10.7%), low/borderline amplification in five cases (0.6%) and true amplification in four cases (0.5%). The correlation between IHC and CISH was statistically significant in CIN2, CIN3 and invasive cervical carcinoma specimens. When present, Her‐2/neu positivity is more commonly seen in higher grades of cervical dysplasia and in carcinoma. However, this large TMA study shows that HER2/neu oncoprotein expression and HER2/neu gene amplification overall are uncommon events in cervical neoplasia. This provides compelling evidence that HER2/neu plays no major role in the development and progression of cervical neoplasia.
Sarcomeres are added in series to emphysematous rat diaphragm after lung volume reduction surgery.

STUDY OBJECTIVES The diaphragm adapts to its shortened state in experimental emphysema primarily by losing sarcomeres in series, thus reducing its optimal operating length. One would expect improved diaphragmatic function after lung volume reduction surgery (LVRS) only if the muscle can readapt to its elevated, lengthened postoperative position by either adding back sarcomeres or lengthening sarcomeres. We used a model of elastase-induced emphysema in rats to test the hypothesis that sarcomere addition occurs following LVRS. DESIGN A cohort of emphysematous rats was created by the intratracheal instillation of elastase. Five months after the instillation, one group of rats underwent measurement of in situ costal diaphragm length via laparotomy, the determination of optimal muscle fiber operating length (Lo) on stimulated diaphragm strips in vitro, and the measurement of sarcomere length by electron microscopy on strips fixed at Lo. Another group of rats underwent LVRS or sham sternotomy 5 months after the instillation, and 5 months following the operation these animals underwent the same series of diaphragmatic studies. RESULTS Lo was significantly greater in rats that underwent LVRS than those that underwent sternotomy (mean [+/- SE] Lo after LVRS, 2.50 +/- 0.08 cm; mean Lo after sternotomy, 2.27 +/- 0.06 cm; p = 0.013). There was no significant difference in sarcomere lengths between the two groups (2.95 +/- 0.04 vs 3.04 +/- 0.04 microm, respectively; p = 0.10). Using Lo as the length basis, the mean sarcomere number was calculated to be 8,712 +/- 192 in animals that had undergone LVRS and 7,144 +/- 249 in animals that had undergone sternotomy (p < 0.001). CONCLUSION Sarcomere length is not significantly altered but sarcomeres are added in series following LVRS in this experimental model of emphysema/LVRS. It is likely that this sarcomere addition is a prerequisite to the improvement in inspiratory muscle function that has been observed following LVRS in humans.
Novel formulation of solid lipid microparticles of curcumin for anti-angiogenic and anti-inflammatory activity for optimization of therapy of inflammatory bowel disease.

OBJECTIVES This project was undertaken with a view to optimize the treatment of inflammatory bowel disease through a novel drug delivery approach for localized treatment in the colon. Curcumin has poor aqueous solubility, poor stability in the gastrointestinal tract and poor bioavailability. The purpose of the study was to prepare and evaluate the anti-inflammatory activity of solid lipid microparticles (SLMs) of curcumin for the treatment of inflammatory bowel disease in a colitis-induced rat model by a colon-specific delivery approach. METHODS We have developed a novel formulation approach for treating experimental colitis in the rat model. SLMs of curcumin were prepared with various lipids, such as palmitic acid, stearic acid and soya lecithin, with an optimized percentage of poloxamer 188. The SLMs of curcumin were characterized for particle size, drug content, drug entrapment, in-vitro release, surface morphology and infrared, differential scanning calorimetry and X-ray studies. The colonic delivery system of SLM formulations of curcumin were further investigated for their anti-angiogenic and anti-inflammatory activity using chick embryo and rat colitis models. KEY FINDINGS Particle size, drug content, drug entrapment and in-vitro release studies showed that formulation F4 containing one part stearic acid and 0.5% surfactant had the smallest diameter of 108 microm, 79.24% entrapment and exhibited excellent in-vitro release characteristics when compared with other formulations and pure curcumin. SLMs of curcumin (F4) proved to be a potent angio-inhibitory compound, as demonstrated by inhibition of angiogenesis in the chorioallantoic membrane assay. Rats treated with curcumin and its SLM complex showed a faster weight gain compared with dextran sulfate solution (DSS) control rats. The increase in whole colon length appeared to be significantly greater in SLM-treated rats when compared with pure curcumin and DSS control rats. An additional finding in the DSS-treated rats was chronic cell infiltration with predominance of eosinophils. Decreased mast cell numbers in the mucosa of the colon of SLMs of curcumin and pure curcumin-treated rats was observed. CONCLUSIONS The degree of colitis caused by administration of DSS was significantly attenuated by colonic delivery of SLMs of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for inflammatory bowel disease patients.
Knowledge of Deaths in Hotel Rooms Diminishes Perceived Value and Elicits Guest Aversion

Guest deaths are an inevitable aspect of the hospitality industry. In Study 1, participants read a vignette in which the previous guest died of natural causes, suicide, or homicide. Those who learned of a death (a) saw the room as less valuable, (b) opted to stay in a more basic room in which no death occurred, despite both rooms being offered for free, and (c) anticipated feeling uneasy when imagining an overnight stay. In Study 2, we investigated the persistence of this bias. Perceived room value and anticipatory well-being can be expected to return to baseline levels only many years after the death event. Similar to “stigmatized properties” in real estate, these data confirm an irrational and recalcitrant cognitive bias surrounding consumers’ views of death-affected hotel rooms.
Comparative Study Between Similarly Processed ${\rm YBa}_{2}{\rm Cu}_{3}{\rm O}_{7-{\rm x}}$ Films With  ${\rm Y}_{2}{\rm BaCuO}_{5}$ or ${\rm BaSnO}_{3}$ Additions

A special YBa<sub>2</sub>Cu<sub>3</sub>O<sub>7-x</sub> (YBCO) target with a thin sector of second phase material, in this case either Y<sub>2</sub>BaCuO<sub>5</sub> (Y211) or BaSnO<sub>3</sub> (BSO), was used to deposit YBCO films with non-layered nanoparticles on single crystal LaAlO<sub>3</sub> and biaxially textured Ni-5 at. % W substrates buffered with CeO<sub>2</sub> and YSZ layers(coated conductors). Although identical processing conditions were used, TEM images indicated that random Y211 nanoparticles in the case of YBCO + Y211, and evenly spaced BSO nanocolumns in the case of YBCO+BSO, form in the YBCO films. While YBCO plane buckling was observed at many places in the case of YBCO + Y211, a high density of stacking faults and dislocations were observed in the case of YBCO+BSO near the BSO columns. In transport critical current density (<i>Jc</i>) angular dependence measurements, the absence of nanocolumns in YBCO + Y211 films resulted in the absence of a peak at 0deg , <i>Jc</i>(<i>H</i>//<i>c</i>) , in <i>Jc</i> vs. thetas plots, as compared to a clear peak at 0deg observed in YBCO+BSO films with the nanocolumns. The in-field <i>Jc</i> measurements indicated small low-field <i>Jc</i> enhancements at 77 K in YBCO + Y211 films but more than an order of magnitude improvement in high-field <i>Jc</i> in YBCO + BSO films due to the differences in the microstructures.
Neopterin and 7,8-Dihydroneopterin Interfere With Low Density Lipoprotein Oxidation Mediated by Peroxynitrite and/or Copper

Low density lipoprotein (LDL) oxidation within the artery wall likely represents a key event in the formation of atherosclerotic lesions. Oxidatively modified LDL particles exert chemotactic properties on macrophages, and the uncontrolled uptake of modified LDL by macrophages leads to the formation of lipid-loaded foam cells, a hallmark of early stage atherosclerosis. Human macrophages stimulated by interferon- n generate reactive oxygen species (ROS), neopterin, and 7,8-dihydroneopterin. Higher concentrations of neopterin were found in atherosclerosis, and earlier studies have provided evidence that these neopterin derivatives are able to interfere with reactive species. We therefore investigated whether they also modulate LDL oxidation mediated by Cu(II) and/or peroxynitrite (ONOO m ). By means of UV-absorption recording the formation of conjugated dienes in the course of lipid oxidation as well as by measuring the relative electrophoretic mobility of oxidized LDL, we found that neopterin is capable of enhancing ONOO m - as well as Cu(II)-mediated LDL oxidation, whereas 7,8-dihydroneopterin mainly protects LDL from oxidation. However, in case of Cu(II)-mediated LDL oxidation, an initial prooxidative effect of 7,8-dihydroneopterin could be observed. We hypothesize that 7,8-dihydroneopterin may chemically reduce Cu(II) to Cu(I) thereby increasing its oxidative capacity. After total reduction of Cu(II), excess 7,8-dihydroneopterin may block the oxidative potential of Cu(I) and thus decrease the oxidation of LDL. These findings confirm the general behavior of pteridines in redox processes and suggest an in vivo contribution to the process of LDL oxidation.
In Vitro Activity of a Novel Broad-Spectrum Antifungal, E1210, Tested against Aspergillus spp. Determined by CLSI and EUCAST Broth Microdilution Methods

ABSTRACT E1210 is a first-in-class broad-spectrum antifungal that suppresses hyphal growth by inhibiting fungal glycophosphatidylinositol (GPI) biosynthesis. In the present study, we extend these findings by examining the activity of E1210 and comparator antifungal agents against Aspergillus spp. by using the methods of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to test wild-type (WT) as well as amphotericin B (AMB)-resistant (-R) and azole-R strains (as determined by CLSI methods). Seventy-eight clinical isolates of Aspergillus were tested including 20 isolates of Aspergillus flavus species complex (SC), 22 of A. fumigatus SC, 13 of A. niger SC, and 23 of A. terreus SC. The collection included 15 AMB-R (MIC, ≥2 μg/ml) isolates of A. terreus SC and 10 itraconazole-R (MIC, ≥4 μg/ml) isolates of A. fumigatus SC (7 isolates), A. niger SC (2 isolates), and A. terreus SC (1 isolate). Comparator antifungal agents included anidulafungin, caspofungin, amphotericin B, itraconazole, posaconzole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparators. The essential agreement (EA; ±2 log2 dilution steps) was 100% for all comparisons with the exception of posaconazole versus A. terreus SC (EA = 91.3%). The minimum effective concentration (MEC)/MIC90 values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, and voriconazole, respectively, were as follows for each species: for A. flavus SC, 0.03, ≤0.008, 0.12, 1, 1, and 1; for A. fumigatus SC, 0.06, 0.015, 0.12, >8, 1, and 4; for A. niger SC, 0.015, 0.03, 0.12, 4, 1, and 2; and for A. terreus SC, 0.06, 0.015, 0.12, 1, 0.5, and 1. E1210 was very active against AMB-R strains of A. terreus SC (MEC range, 0.015 to 0.06 μg/ml) and itraconazole-R strains of A. fumigatus SC (MEC range, 0.03 to 0.12 μg/ml), A. niger SC (MEC, 0.008 μg/ml), and A. terreus SC (MEC, 0.015 μg/ml). In conclusion, E1210 was a very potent and broad-spectrum antifungal agent regardless of in vitro method applied, with excellent activity against AMB-R and itraconazole-R strains of Aspergillus spp.
Urinary isolates of apramycin-resistant Escherichia coli and Klebsiella pneumoniae from Dublin

SUMMARY Twenty-two gentamicin-resistant urinary isolates of Escherichia coli and five gentamicin-resistant urinary isolates of Klebsiella pneumoniae from a Dublin hospital were examined for resistance to the veterinary aminoglycoside antibiotic apramycin. Five isolates of E. coli and one isolate of K. pneumoniae were found to be resistant. The apramycin-resistant isolates, which were also resistant to the veterinary anthelmintic agent hygromycin B, hybridized with a DNA probe for the gene encoding the enzyme 3-N-aminoglycoside acetyltransferase type IV (AAC(3)IV). Resistance to apramycin and hygromycin B was co-transferable in four of the five isolates of E. coli and the isolate of K. pneumoniae. In one isolate of E. coli apramycin resistance was not transferable. On the basis of their restriction enzyme digestion profiles and the antimicrobial resistance traits encoded, the transferable plasmids encoding resistance to apramycin and hygromycin B comprised three distinct types. Genetic linkage between the gene encoding AAC(3)IV and genes encoding resistance to ampicillin and either tetracycline or trimethoprim, means that the relatively widespread use of these antimicrobial agents provides a selective pressure for the persistence of resistance to apramycin and gentamicin even in the absence of bacterial exposure to aminoglycosides.