Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiological effects of Na+/Ca2+exchanger knockdown by antisense oligodeoxynucleotides in arterial myocytes.

Antisense oligodeoxynucleotides (AS-oligos) targeted to the Na+/Ca2+exchanger (NCX) inhibit NCX-mediated Ca2+ influx in mesenteric artery (MA) myocytes [ Am. J. Physiol.269 ( Cell Physiol. 38): C1340-C1345, 1995]. Here, we show AS-oligo knockdown of NCX-mediated Ca2+ efflux. In initial experiments, the cytosolic free Ca2+ concentration ([Ca2+]cyt) was raised, and sarcoplasmic reticulum (SR) Ca2+ sequestration was blocked with caffeine and cyclopiazonic acid; the extracellular Na+-dependent (NCX) component of Ca2+ efflux was then selectively inhibited in AS-oligo-treated cells but not in controls (no oligos or nonsense oligos). In contrast, the La3+-sensitive (plasmalemma Ca2+ pump) component of Ca2+ efflux was unaffected in AS-oligo-treated cells. Knockdown of NCX activity was reversed by incubating AS-oligo-treated cells in normal media for 5 days. Transient [Ca2+]cytelevations evoked by serotonin (5-HT) at 15-min intervals in AS-oligo-treated cells were indistinguishable from those in controls. When cells were stimulated every 3 min, however, the peak amplitudes of the second and third responses were larger, and [Ca2+]cytreturned to baseline more slowly, in AS-oligo-treated cells than in controls. Peak 5-HT-evoked responses in the controls, but not AS-oligo-treated cells, were augmented more than twofold in Na+-free media. This implies that NCX is involved in Na+ gradient modulation of SR Ca2+ stores and cell responsiveness. The repetitive stimulation data suggest that the NCX may be important during tonic activation of arterial myocytes.
Assessment of vitamin B-12, folate, and vitamin B-6 status and relation to sulfur amino acid metabolism in neonates.

BACKGROUND Total serum homocysteine (tHcy) has been used as an indicator of intracellular vitamin B-12, vitamin B-6, and folate status in adults, but data for neonates and infants are lacking. Vitamin B-12 deficiency may have fatal effects on neurologic development in infants; therefore, early diagnosis is crucial. OBJECTIVE Our aim was to provide a reference range for tHcy in neonates and to explore the relation of tHcy to 1) serum vitamin concentrations, 2) the product of the transsulfuration pathway (cysteine), and 3) nutritional factors. DESIGN tHcy, cysteine, folate, vitamin B-12, and vitamin B-6 were measured in 123 healthy, breast-fed neonates. The influence of nutrition (formula or human milk) on these variables was investigated in 60 infants. RESULTS The mean (+/-SD) tHcy concentration was 7.8 +/- 3.1 micromol/L. tHcy showed a linear association with log vitamin B-12 (r = -0.64, P: < 0. 001), red blood cell folate (r = -0.33, P: < 0.001), and cysteine (r = 0.36, P: < 0.001). The strongest linear association was found between tHcy and the ratio of log cysteine to log vitamin B-12 (r = 0.71, P: < 0.0001). We found more neonates with probable tissue deficiencies of vitamin B-12 and folate on the basis of tHcy measurements than was expected from the analysis of serum vitamin concentrations alone (15.4% compared with 9.7%). Breast-fed infants had significantly lower vitamin B-12 concentrations and significantly higher serum tHcy and cysteine concentrations and ratios of log cysteine to log vitamin B-12 than did formula-fed infants (P: < 0.001). CONCLUSIONS tHcy can be used as a functional indicator of vitamin B-12 and folate status in neonates. The ratio of cysteine to vitamin B-12 can be used as an additional index of impaired intracellular Hcy metabolism. tHcy and cysteine concentrations in infants are affected by nutritional factors.
Daily rhythms in Fos activity in the rat ventrolateral preoptic area and midline thalamic nuclei.

The present experiment investigated the expression of the nuclear phosphoprotein Fos over the 24-h light-dark cycle in regions of the rat brain related to sleep and vigilance, including the ventrolateral preoptic area (VLPO), the paraventricular thalamic nucleus (PVT), and the central medial thalamic nucleus (CMT). Immunocytochemistry for Fos, an immediate-early gene product used as an index of neuronal activity, was carried out on brain sections from rats perfused at zeitgeber time (ZT) 1, ZT 5, ZT 12.5, and ZT 17 (lights on ZT 0-ZT 12). The number of Fos-immunopositive (Fos+) cells in the VLPO was elevated at ZT 5 and 12.5 (i.e., during or just after the rest phase of the cycle). Fos+cell number increased at ZT 17 and ZT 1 in the PVT and CMT, 180° out of phase with the VLPO. A positive correlation was found between the numbers of Fos+ cells in the PVT and CMT, and Fos expression in each thalamic nucleus was negatively correlated with VLPO Fos+ cell number. The VLPO, PVT, and CMT may integrate circadian and homeostatic influences to regulate the sleep-wake cycle.
Simulating tactile signals from the whole hand with millisecond precision

Significance When we grasp an object, thousands of tactile nerve fibers become activated and inform us about its physical properties (e.g., shape, size, and texture). Although the properties of individual fibers have been described, our understanding of how object information is encoded in populations of fibers remains primitive. To fill this gap, we have developed a simulation of tactile fibers that incorporates much of what is known about skin mechanics and tactile nerve fibers. We show that simulated fibers match biological ones across a wide range of conditions sampled from the literature. We then show how this simulation can reveal previously unknown ways in which populations of nerve fibers cooperate to convey sensory information and discuss the implications for bionic hands. When we grasp and manipulate an object, populations of tactile nerve fibers become activated and convey information about the shape, size, and texture of the object and its motion across the skin. The response properties of tactile fibers have been extensively characterized in single-unit recordings, yielding important insights into how individual fibers encode tactile information. A recurring finding in this extensive body of work is that stimulus information is distributed over many fibers. However, our understanding of population-level representations remains primitive. To fill this gap, we have developed a model to simulate the responses of all tactile fibers innervating the glabrous skin of the hand to any spatiotemporal stimulus applied to the skin. The model first reconstructs the stresses experienced by mechanoreceptors when the skin is deformed and then simulates the spiking response that would be produced in the nerve fiber innervating that receptor. By simulating skin deformations across the palmar surface of the hand and tiling it with receptors at their known densities, we reconstruct the responses of entire populations of nerve fibers. We show that the simulated responses closely match their measured counterparts, down to the precise timing of the evoked spikes, across a wide variety of experimental conditions sampled from the literature. We then conduct three virtual experiments to illustrate how the simulation can provide powerful insights into population coding in touch. Finally, we discuss how the model provides a means to establish naturalistic artificial touch in bionic hands.
Variability in Patterns of Recurrence After Resection of Primary Retroperitoneal Sarcoma (RPS): A Report on 1007 Patients From the Multi-institutional Collaborative RPS Working Group

Background:Retroperitoneal sarcomas (RPS) are rare tumors composed of several well defined histologic subtypes. The aim of this study was to analyze patterns of recurrence and treatment variations in a large population of patients, treated at reference centers. Methods:All consecutive patients with primary RPS treated at 6 European and 2 North American institutions between January 2002 and December 2011 were included. Five, 8, and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariate analyses for OS, CCI of LR, and DM were performed. Results:In all, 1007 patients were included. Median follow-up was 58 months (first and third quartile range 36–90). The 5, 8, and 10-year OS were 67% [95% confidence interval (CI), 63, 70), 56% (95% CI, 52, 61), and 46% (95% CI, 40, 53). The 5, 8, and 10-year CCI of LR and DM were 25.9 (95% CI, 23.1, 29.1), 31.3 (95% CI, 27.8, 35.1), 35% (95% CI, 30.5, 40.1), and 21% (95% CI, 18.4, 23.8%), 21.6 (95% CI, 19.0, 24.6), and 21.6 (95% CI, 19.0, 24.6), respectively. Tumour size, histologic subtype, malignancy grade, multifocality, and completeness of resection were significant predictors of outcome. Patterns of recurrence varied depending on histologic subtype. Different treatment policies at participating institutions influenced LR of well differentiated liposarcoma without impacting OS, whereas discrepancies in adjuvant systemic therapies did not impact LR, DM, or OS of leiomyosarcoma. Conclusions:Reference centers are critical to outcomes of RPS patients, as the management strategy requires specific expertise. Histologic subtype predicts patterns of recurrence and should inform management decision. A prospective international registry is under preparation, to further define our understanding of this disease.
Treatment and prevention of HIV infection with long-acting antiretrovirals

ABSTRACT Introduction: Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance. Unfortunately, drug adherence is often suboptimal and tends to decline over time. Areas covered: New drugs, formulations and delivery systems are being developed for extended-release of antiretrovirals. At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal rings and tenofovir alafenamide subdermal implants are the products in more advanced stages of clinical development. Their pharmacokinetics/dynamics and safety/efficacy are reviewed. Expert commentary: In the absence of eradicative therapy for individuals with HIV infection and protective vaccines for persons at risk, long-term antiretroviral therapy is the best approach for preventing disease progression in patients and halting transmissions, either as result of ‘treatment as prevention’ for HIV carriers or ‘pre-exposure prophylaxis’ for uninfected individuals at risk. In all these scenarios, the advent of long-acting antiretrovirals will expand options for overcoming the challenge of suboptimal drug adherence and reduce the burden of HIV infection.
Research progress in the modification of graphene

Based on the research progress of modification of graphene material at home and abroad,the methods of modification of graphene are introduced from the surface modification and the electronic properties modification,respectively.The methods of surface modification contain the covalent functionalization and non-covalent functionalization;the methods of electronic properties modification contain doping and ion bombardment.Finally,the advantages and disadvantages of various modification methods are discussed,and the further development of modification of graphene is pointed out on the basis of original modification methods.
Peroxynitrite inhibits amiloride-sensitive Na+ currents in Xenopus oocytes expressing αβγ-rENaC.

We examined the effect of peroxynitrite (ONOO-) on the cloned rat epithelial Na+ channel (αβγ-rENaC) expressed in Xenopusoocytes. 3-Morpholinosydnonimine (SIN-1) was used to concurrently generate nitric oxide (⋅ NO) and superoxide ([Formula: see text] ⋅), which react to form ONOO-, a species known to promote protein nitration and oxidation. Under control conditions, oocytes displayed an amiloride-sensitive whole cell conductance of 7.4 ± 2.8 (SE) μS. When incubated at 18°C with SIN-1 (1 mM) for 2 h (final ONOO- concentration = 10 μM), the amiloride-sensitive conductance was reduced to 0.8 ± 0.5 μS. To evaluate whether the observed inhibition was due to ONOO-, as opposed to ⋅ NO, we also exposed oocytes to SIN-1 in the presence of urate (500 μM), a scavenger of ONOO- and superoxide dismutase, which scavenges[Formula: see text] ⋅, converting SIN-1 from an ONOO- to an ⋅ NO donor. Under these conditions, conductance values remained at control levels following SIN-1 treatment. Tetranitromethane, an agent that oxidizes sulfhydryl groups at pH 6, also inhibited the amiloride-sensitive conductance. These data suggest that oxidation of critical sulfhydryl groups within rENaC by ONOO- directly inhibits channel activity.
Bioavailability of soybean isoflavones from aglycone and glucoside forms in American women.

BACKGROUND Test results on the bioavailability of isoflavones in the aglycone or glucoside form in Eastern and Western human subjects are contradictory. OBJECTIVE The objective was to investigate the bioavailability of the soy isoflavones daidzein and genistein in American women with typical American dietary habits after ingestion of the aglycone or glucoside form of isoflavones. DESIGN Fifteen American women aged 46 +/- 6 y participated in a randomized, double-blind study. Blood samples were collected 0, 1, 2, 4, 8, 12, 24, and 48 h after consumption of aglycone or glucoside tablets with breakfast. The plasma curves for daidzein, genistein, and equol were constructed and the postprandial maximum concentration (C(max)), time to the maximum concentration (t(max)), and area under the curve (AUC) were determined. RESULTS Isoflavone concentrations peaked early (1-2 h) in plasma and peaked again at 4-8 h. Mean C(max), t(max), and AUC values for genistein were not significantly different after ingestion of aglycone or glucoside. However, C(max) and AUC values, but not t(max), were significantly higher for daidzein after aglycone ingestion, which was partly due to its higher content in the aglycone tablets. Equol appeared after 4 h and remained elevated after 48 h. Despite a higher content of daidzein in the aglycone tablets, the AUC for equol was significantly higher after ingestion of the glucoside tablets, probably because of the metabolic action of intestinal bacteria during the long intestinal transit time of glucoside. CONCLUSION The apparent bioavailability of genistein and daidzein is not different when consumed as either aglycone or glucoside by American women.
Docosahexaenoic acid supply in pregnancy affects placental expression of fatty acid transport proteins.

BACKGROUND Better understanding of the mechanisms involved in docosahexaenoic acid (DHA) transfer to the neonate may contribute to improve dietary support for infants born prematurely to mothers with placental lipid transport disorders. OBJECTIVE We studied whether DHA supplements modify the messenger RNA (mRNA) expression of placental lipid transport proteins to allow a selective transfer of DHA to the fetus. DESIGN Healthy pregnant women (n = 136) received, in a double-blind randomized trial, 500 mg DHA + 150 mg eicosapentaenoic acid, 400 microg 5-methyl-tetrahydrofolic acid, 500 mg DHA + 400 microg 5-methyl-tetrahydrofolic acid, or placebo during the second half of gestation. We analyzed the fatty acid composition of maternal and cord blood phospholipids and of placenta; we quantified placental mRNA expression of fatty acid-transport protein 1 (FATP-1), FATP-4, FATP-6, fatty acid translocase, fatty acid-binding protein (FABP) plasma membrane, heart-FABP, adipocyte-FABP, and brain-FABP. RESULTS The mRNA expression of the lipid carriers assayed did not differ significantly between the 4 groups. However, the mRNA expression of FATP-1 and FATP-4 in placenta was correlated with DHA in both maternal plasma and placental phospholipids, although only FATP-4 expression was significantly correlated with DHA in cord blood phospholipids. Additionally, the mRNA expression of several membrane lipid carriers was correlated with EPA and DHA in placental triacylglycerols and with EPA in placental free fatty acids. CONCLUSIONS Correlation of the mRNA expression of the membrane placental proteins FATP-1 and especially of FATP-4 with maternal and cord DHA leads us to conclude that these lipid carriers are involved in placental transfer of long-chain polyunsaturated fatty acids.
Intakes of energy and macronutrients and the risk of benign prostatic hyperplasia.

BACKGROUND Benign prostatic hyperplasia (BPH) is a common disease of older men. Although the etiology remains unclear, nutritional factors may have an effect on the disease. OBJECTIVE Because the literature on the relations between macronutrient intakes and BPH risk is limited, we examined these relations among men in the Health Professionals Follow-up Study. DESIGN We followed men aged 40-75 y from baseline in 1986 to 1994. Total BPH cases (n = 3523) comprised men who reported BPH surgery (n = 1589) or who did not undergo surgery but scored 15-35 points on the lower urinary tract symptom questionnaire of the American Urological Association (n = 1934); non-cases were men who scored < or = 7 points (n = 24388). Odds ratios (ORs) and 95% CIs were calculated by using multivariate logistic regression. RESULTS The ORs rose with increasing total energy intake in a comparison of the highest and lowest quintiles for total BPH (OR: 1.29; 95% CI: 1.14, 1.45) and symptoms of BPH (1.43; 1.23, 1.66). Energy-adjusted total protein intake was positively associated with total BPH (1.18; 1.05, 1.33) and BPH surgery (1.26; 1.06, 1.49). Energy-adjusted total fat intake was not associated with risk of total BPH, but intakes of eicosapentaenoic, docosahexaenoic, and arachidonic acids were associated with a moderate increase in risk of total BPH. CONCLUSIONS We observed modest direct associations between BPH and intakes of total energy, protein, and specific long-chain polyunsaturated fatty acids. Because eicosapentaenoic, docosahexaenoic, and arachidonic acids are highly unsaturated fatty acids, our findings support a possible role of oxidative stress in the etiology of BPH.
Interregulation of CDKA/CDK1 and the Plant-Specific Cyclin-Dependent Kinase CDKB in Control of the Chlamydomonas Cell Cycle[OPEN]

Chlamydomonas CDKA and CYCA1 are dispensable for mitosis, but the plant-specific CDKB, probably in complex with CYCB1, promotes most events of mitosis and downregulates CDKA following cell division. The cyclin-dependent kinase CDK1 is essential for mitosis in fungi and animals. Plant genomes contain the CDK1 ortholog CDKA and a plant kingdom-specific relative, CDKB. The green alga Chlamydomonas reinhardtii has a long G1 growth period followed by rapid cycles of DNA replication and cell division. We show that null alleles of CDKA extend the growth period prior to the first division cycle and modestly extend the subsequent division cycles, but do not prevent cell division, indicating at most a minor role for the CDK1 ortholog in mitosis in Chlamydomonas. A null allele of cyclin A has a similar though less extreme phenotype. In contrast, both CDKB and cyclin B are essential for mitosis. CDK kinase activity measurements imply that the predominant in vivo complexes are probably cyclin A-CDKA and cyclin B-CDKB. We propose a negative feedback loop: CDKA activates cyclin B-CDKB. Cyclin B-CDKB in turn promotes mitotic entry and inactivates cyclin A-CDKA. Cyclin A-CDKA and cyclin B-CDKB may redundantly promote DNA replication. We show that the anaphase-promoting complex is required for inactivation of both CDKA and CDKB and is essential for anaphase. These results are consistent with findings in Arabidopsis thaliana and may delineate the core of plant kingdom cell cycle control that, compared with the well-studied yeast and animal systems, exhibits deep conservation in some respects and striking divergence in others.
Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults.

BACKGROUND Mandatory folic acid fortification of food is effective in reducing neural tube defects and may even reduce stroke-related mortality, but it remains controversial because of concerns about potential adverse effects. Thus, it is virtually nonexistent in Europe, albeit many countries allow food fortification on a voluntary basis. OBJECTIVE The objective of the study was to examine the effect of a voluntary but liberal food fortification policy on dietary intake and biomarker status of folate and other homocysteine-related B vitamins in a healthy population. DESIGN The study was a cross-sectional study. From a convenience sample of 662 adults in Northern Ireland, those who provided a fasting blood sample and dietary intake data were examined (n = 441, aged 18-92 y). Intakes of both natural food folate and folic acid from fortified foods were estimated; we used the latter to categorize participants by fortified food intake. RESULTS Fortified foods were associated with significantly higher dietary intakes and biomarker status of folate, vitamin B-12, vitamin B-6, and riboflavin than were unfortified foods. There was no difference in natural food folate intake (range: 179-197 microg/d) between the fortified food categories. Red blood cell folate concentrations were 387 nmol/L higher and plasma total homocysteine concentrations were 2 micromol/L lower in the group with the highest fortified food intake (median intake: 208 microg/d folic acid) than in the nonconsumers of fortified foods (0 microg/d folic acid). CONCLUSIONS These results show that voluntary food fortification is associated with a substantial increase in dietary intake and biomarker status of folate and metabolically related B vitamins with potential beneficial effects on health. However, those who do not consume fortified foods regularly may have insufficient B vitamin status to achieve the known and potential health benefits.
Semiconductor plasmonic nanolasers: current status and perspectives

Scaling down semiconductor lasers in all three dimensions holds the key to the development of compact, low-threshold, and ultrafast coherent light sources, as well as integrated optoelectronic and plasmonic circuits. However, the minimum size of conventional semiconductor lasers utilizing dielectric cavity resonators (photonic cavities) is limited by the diffraction limit. To date, surface plasmon amplification by stimulated emission of radiation (spaser)-based plasmonic nanolaser is the only photon and plasmon-emitting device capable of this remarkable feat. Specifically, it has been experimentally demonstrated that the use of plasmonic cavities based on metal-insulator-semiconductor (MIS) nanostructures can indeed break the diffraction limit in all three dimensions. In this review, we present an updated overview of the current status for plasmonic nanolasers using the MIS configuration and other related metal-cladded semiconductor microlasers. In particular, by using composition-varied indium gallium nitride/gallium nitride core–shell nanorods, it is possible to realize all-color, single-mode nanolasers in the full visible wavelength range with ultralow continuous-wave (CW) lasing thresholds. The lasing action in these subdiffraction plasmonic cavities is achieved via a unique auto-tuning mechanism based on the property of weak size dependence inherent in plasmonic nanolasers. As for the choice of metals in the plasmonic structures, epitaxial silver films and giant colloidal silver crystals have been shown to be the superior constituent materials for plasmonic cavities due to their low plasmonic losses in the visible and near-infrared (NIR) spectral regions. In this review, we also provide some perspectives on the challenges and opportunities in this exciting new research frontier.