Miracle-dz/UniFAR-FTUs huggingface dataset:
P2 purinoceptor‐mediated depolarization of rat supraoptic neurosecretory cells in vitro.

1. Intracellular recordings were obtained from supraoptic magnocellular neurosecretory cells (MNCs) in superfused explants of rat hypothalamus. Application of ATP and UTP, but not adenosine, produced TTX‐insensitive depolarizations accompanied by increases of input conductance. 2. The P2X agonists alpha,beta‐methylene ATP, beta,gamma‐methylene ATP and 2‐methylthio ATP mimicked the effects of ATP in > 77% of the cells tested. Depolarizing responses to ATP were reversibly inhibited by PPADS (pyridoxal‐phosphate‐6‐azophenyl‐2',4'‐ disulphonic acid; IC50 approximately 0.5 microM), a selective P2X antagonist. 3. The reversal potential of responses to ATP (‐37 mV) was not strongly affected by intracellular Cl‐ injection or by removal of Cl‐ from the external solution. The reversal potential of responses to the most potent P2X agonist, alpha,beta‐methylene ATP, was ‐29 mV. These values suggest the involvement of non‐selective cationic channels, a finding which is consistent with the ionotropic cationic channel structure of cloned P2X purinoceptors. 4. The reversal potential of UTP‐mediated responses (‐33 mV) was also consistent with the involvement of non‐selective cationic channels. Since cloned P2U receptors display homology with G‐protein‐coupled receptors, cationic channels modulated by UTP are probably different from those mediating P2X responses.
Comparison of Azelnidipine and Trichlormethiazide in Japanese Type 2 Diabetic Patients with Hypertension: The COAT Randomized Controlled Trial

Objective This study compared the efficacy and safety of azelnidipine with that of trichlormethiazide in Japanese type 2 diabetic patients with hypertension. Methods In a multicenter, open-label trial, 240 patients with adequately controlled diabetes (HbA1c ≤ 7.0%) under lifestyle modification and/or administration of hypoglycemic agents and inadequately controlled hypertension (systolic blood pressure [sBP] ≥ 130 mmHg or diastolic blood pressure [dBP] ≥ 80 mmHg) who were being treated with olmesartan were enrolled. Participants were randomly assigned to an azelnidipine group or a trichlormethiazide group and were followed up for 48 weeks. Main outcome measure was the difference in the change in HbA1c levels from the baseline values at 48 weeks between these two groups. Results Of the 240 subjects that were enrolled, 209 subjects (azelnidipine group: 103 patients, trichlormethiazide group: 106 patients) completed this trial. At 48 weeks, the following changes were observed in the azelnidipine and trichlormethiazide groups, respectively: HbA1c levels, 0.19 ± 0.52% and 0.19 ± 0.54%; sBP/dBP, -10.7 ± 9.6/-6.6 ± 6.6 mmHg and -7.1 ± 7.7/-3.3 ± 6.1 mmHg (P < 0.001 for both sBP and dBP). In both groups, dizziness (12 patients [11.7%] and 16 patients [15.1%]) and edema (16 patients [15.5%] and 7 patients [6.6%], P = 0.047) were observed during the 48-week follow-up period. Conclusions Azelnidipine was more effective for controlling blood pressure than trichlormethiazide in Japanese type 2 diabetes patients, whereas trichlormethiazide was more effective for reducing albuminuria than azelnidipine. Both of these agents, however, similarly exacerbated glycemic control in type 2 diabetic patients with hypertension. Trial Registration UMIN 000006081.
Biotechnological significance of actinobacterial research in India

Actinobacteria are of special biotechnological interest since they are known to produce chemically diverse compounds with a wide range of biological activity. This distinct clade of Gram-positve bacteria include some of the key antibiotic producers and are also sources of several bioactive compounds, established commercially. The class Actinobacteria holds some of the resilient species, capable of growing in extreme, hostile and polluted environments. Their adaptation has been the outcome of several chemical entities which are answers to a number of medicinal and industrial questions of today. In India, actinobacterial research in both marine and terrestrial ecosystems has prospered significantly in past few decades. This valuable class contains large number of genera and demands more attention for exploration. Though substantial work in this field has been carried out, the diversity from the extreme environments in the Indian Peninsula remain unexplored. Marine actinobacterial research has been restricted to the coastal ecosystem while the deep sea oceanic floors remain untapped . Substantial bioprospecting of actinobacteria for bioactive molecules, has not been explored in extremophilic environments in India and the molecular mechanisms for the production of various bioactive compounds are yet to be reported. The present review enlists the prolific metabolites from culturable actinobacteria and attempts have been made to focus on the potentially feasible aspects of actinobacterial research in this field.
Mechanisms of epigenetic inheritance: Copying of Polycomb repressed chromatin

A key problem in gene regulation is how transcription patterns can be stably maintained in dividing cells. The formation and propagation of chromatin structures is believed to underlie stable gene expression patterns, including those maintained by Polycomb Group proteins. Recent studies focused on how Polycomb Group proteins and the chromatin structures they create behave during DNA replication and have begun to shed light onto mechanisms by which chromatin structures may be propagated through S-phase. These studies suggest that both segregation of chromatin features to newly replicated chromatin and a feedback loop consisting of histone modification and recognition of this modification may contribute to inheritance. Results are discussed in light of other links between Polycomb proteins and DNA replication, and other systems in which maintenance of repression is believed to involve propagation of heritable chromatin structures.
Preoperative fasting induces protection against renal ischemia/reperfusion injury by a corticosterone‐independent mechanism

Three days of fasting protects mice against lethal renal ischemia–reperfusion (I/R) injury. We hypothesize that the protection imposed by fasting is mediated by increased levels of corticosterone, induced by the stress of food deprivation. C57Bl/6 mice were fasted for 3 days after which serum corticosterone levels were determined. Mice underwent a bilateral adrenalectomy (ADX). Ten days later, they were either fasted or given a corticosterone receptor antagonist while fasting. Bilateral renal I/R injury was induced by clamping the artery and vein of the left and right kidney simultaneously for 37 min. Survival and kidney function were determined. Fasting significantly increased corticosterone levels. Only 8% of the ADX mice which were fasted prior to I/R injury survived, whereas all sham‐ADX operated mice survived I/R injury after fasting. After ADX and fasting, 70% of the mice subjected to sham I/R succumbed to the surgical procedure. After fasting with concomitant blockade of the glucocorticoid receptor all animals survived renal I/R. Three days of fasting protects against I/R injury and increases serum corticosterone levels. ADX renders mice incapable of withstanding subsequent abdominal surgery. Glucocorticoid receptor blockade does not interfere with the protective effects of fasting. Thus, the protection against renal I/R injury induced by preoperative fasting is mediated by corticosterone‐independent mechanisms.
Elicitation of Valerenic Acid in the Hairy Root Cultures of Valeriana officinalis L (Valerianaceae)

Purpose: To investigate the effect of magnesium and calcium as abiotic elicitors on Valeriana officinalis hairy roots for scale-up production of valerenic acid. Methods : Hairy roots were established in different explants of Valeriana officinalis via a mikimopine type strain of Agrobacterium rhizogenes ‘A13’. Transgenic status of hairy roots was confirmed by polymerase chain reaction (PCR) analysis of the rolB gene. Hairy roots of 28-day old cultures were exposed to magnesium and calcium (2 to 6-fold concentration of that present in normal Murashige and Skoog (MS) medium for 3 and 7 days. After elicitation, the cultures were grown in MS liquid medium without elicitors for 8 weeks. Valerenic acid content in hairy roots was analysed using high-performance liquid chromatography (HPLC) to determine the best yield conditions. Results: Transformed cultures showed significant differences (p < 0.05) in valerenic acid content. The highest amount of valerenic acid (1.83 ± 0.06 mg/g dry weight (DW) was found in hairy root cultures exposed to 6-fold calcium for 7 days, which was 7.9 times higher than that of control culture (0.23 ± 0.01 mg/g DW). Conclusion: The results show that concentration and exposure time to elicitors are important factors that affect the production of valerenic acid. Key words : Valeriana officinalis, Agrobacterium rhizogenes , Elicitors, Explants, Hairy roots, Valerenic acid, Calcium, Magnesium, rolB gene, Transgenic
Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae

We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media.
Association between gait variability, falls and mobility in people with multiple sclerosis: A specific observation on the EDSS 4.0-4.5 level.

BACKGROUND We previously demonstrated that gait variability increases throughout the disease process in people with multiple sclerosis (PwMS). While gait variability tends to remain steady in the lower levels of disability, a significant increase occurs once patients reach the moderate neurological level. OBJECTIVE To examine the relationship between variability of major spatio-temporal parameters of gait and falls, in PwMS with an expanded disability status scale score of 4.0 and 4.5. METHODS The study included 91 PwMS, 50 women. Gait variability was studied using an electronic mat. Clinical gait measures included the Two-minute walk test, Timed Up and Go test and the Timed 25-foot walk. RESULTS Fifty patients were classified as fallers, 41, non-fallers. The MS fallers presented a higher variability score in the step length (37.3% increase) and single support (28.2% increase) compared to participants in the non-fallers. Additionally, gait variability scores were significantly correlated with clinical walking tests. The strongest correlation scores were for variability of the step length. Pearson's rho scores for the Timed Up and Go test, 2-min walk and Timed 25-foot walk were 0.541, - 0.448 and 0.425, respectively. CONCLUSIONS This study confirms that gait variability is a potential treatment target for PwMS moderately disabled, in order to decrease risk of falls.
Defining the role of PfCRT in Plasmodium falciparum chloroquine resistance

Recent studies have highlighted the importance of a parasite protein referred to as the chloroquine resistance transporter (PfCRT) in the molecular basis of Plasmodium falciparum resistance to the quinoline antimalarials. PfCRT, an integral membrane protein with 10 predicted transmembrane domains, is a member of the drug/metabolite transporter superfamily and is located on the membrane of the intra‐erythrocytic parasite's digestive vacuole. Specific polymorphisms in PfCRT are tightly correlated with chloroquine resistance. Transfection studies have now proven that pfcrt mutations confer verapamil‐reversible chloroquine resistance in vitro and reveal their important role in resistance to quinine. Available evidence is consistent with the view that PfCRT functions as a transporter directly mediating the efflux of chloroquine from the digestive vacuole.
Surgical Site Infections in Spinal Surgery

Surgical site infections (SSIs) are a potentially devastating complication of spine surgery. SSIs are defined by the Centers for Disease Control and Prevention as occurring within 30 days of surgery or within 12 months of placement of foreign bodies, such as spinal instrumentation. SSIs are commonly categorized by the depth of surgical tissue involvement (ie, superficial, deep incisional, or organ and surrounding space). Postoperative infections result in increased costs and postoperative morbidity. Because continued research has improved the evaluation and management of spinal infections, spine surgeons must be aware of these modalities. The controversies in evaluation and management of SSIs in spine surgery will be reviewed.
Synthesis of a Potent G‐Quadruplex‐Binding Macrocyclic Heptaoxazole

A novel G‐quadruplex binder, L1H1‐7OTD (shown in color by atom type), was developed. This macrocyclic heptaoxazole potently and selectively stabilizes telomeric DNA in an intramolecular antiparallel G‐quadruplex conformation. L1H1‐7OTD shows selective cytotoxicity toward HeLa cells, a telomerase‐positive cell line.
Problems of Subject Inclusion in Psychiatric Research: Observations from Research with Psychiatric Inpatients

Abstract: In a recent study of psychiatric disturbance and decision making behaviour12, it was observed that a significant number of psychiatric inpatients experienced difficulties in addressing themselves to the experimental tasks at hand. Despite the large number of studies that have used psychiatric inpatients as subjects, little, if any mention has been made of these difficulties. The following report describes the difficulties that have been observed in the above research project, and examines their possible implications for clinical assessment, research, and for clinical investigations and evaluation of treatment regimes (e.g. effectiveness of particular drug therapies), which use psychiatric inpatient populations as subject sources.
Retinol conversion to retinoic acid is impaired in breast cancer cell lines relative to normal cells.

The bioactivity of retinol (vitamin A) is in part dependent on its metabolism to retinoic acid (RA). We investigated the ability of breast epithelial cells to synthesize RA when challenged with a physiological retinol dose (2 microM). Normal human mammary epithelial cells (HMEC) cultured from reduction mammoplasties were competent in RA synthesis and the ability to synthesize RA was retained by immortal, nontumorigenic breast epithelial cell lines (MTSV1.7, MCF-10F, and 184B5). In contrast, most (five of six) breast cancer cell lines could not synthesize RA or did so at low rates relative to normal cells. A notable exception was the MDA-MB-468 cell line, which was fully competent in RA synthesis. Most (>/=68%) of the RA synthesized by breast cells was recovered from the culture medium. Cellular retinol binding protein and cellular RA binding protein II, both expressed in HMEC, had various expression patterns in the cell lines that did not correlate with the observed differences in RA synthesizing ability. Strong RA induction of the RA hydroxylase P450RAI (CYP26) was confined to ERalpha-positive T47D and MCF-7 breast cancer cells and did not appear to explain the lack of detectable RA levels in these cells since RA remained undetectable when the cells were treated with 5-10 microM liarozole, a P450RAI inhibitor. We hypothesize that retinol bioactivity is impaired in breast cancer cells that cannot synthesize RA. In preliminary support of this hypothesis, we found that retinol (0.5-2 microM) inhibited MCF-10F but not T47D or MCF-7 cell growth.
Foreign Exchange, Fractional Cointegration and the Implied-Realized Volatility Relation

Almost all relevant literature has characterized implied volatility as a biased predictor of realized volatility. This paper provides new time series techniques to assess the validity of this finding within a foreign exchange market context. We begin with the empirical observation that the fractional order of volatility is often found to have confidence intervals that span the stationary/non-stationary boundary. However, no existing fractional cointegration test has been shown to be robust to both regions. Therefore, a new test for fractional cointegration is developed and shown to be robust to the relevant orders of integration. Secondly, employing a dataset that includes the relatively new Euro markets, it is shown that implied and realized volatility are fractionally cointegrated with a slope coefficient of unity. Moreover, the non-standard asymptotic distribution of estimators when using fractionally integrated data is overcome by employing a bootstrap procedure in the frequency domain. Strikingly, tests then show that implied volatility is an unbiased predictor of realized volatility!
Reply

We thank Dr. Smirmaul for his interest in our findings, but advise caution not to over-interpret the data to address a question which would have required an entirely different study design. Specifically, the letter to the editor is strongly focused on effort perception, a variable which was, as expected, not considered as a descriptor by the participants when asked to report evoked sensations (Pollak et al., 2014). In fact, given that the perception of effort requires at least the attempt to activate muscle (or brain neurons), an altered perception would have been rather unusual given the absence of any sort of muscle contraction or task in our study (i.e. there was no required effort to be rated). In addition to having missed this critical fact, we disagree with the main postulate of the letter and need to remind the author about existing evidence documenting an independent role for both central command and muscle afferent feedback in determining the perception of effort during exercise. On the one hand, experiments utilizing curare to increase central command while leaving muscle afferent feedback unchanged during a given task have reported a facilitating effect of central command on effort perception [e.g., (Gandevia & McCloskey, 1977; Gallagher et al., 2001)]. On the other hand, studies utilizing fentanyl to block group III/IV muscle afferents while leaving central command unchanged during exercise document a significant contribution of neural feedback to the perception of effort associated with physical activity [e.g., (Amann et al., 2011; Gagnon et al., 2012)]. Taken together, the line of reasoning used in the letter is refuted by a) the fact that subjects were instructed not to – or attempt to – move their thumb excluded any physical effort to be rated/perceived (which explains the lack of this variable on the participant-driven list of descriptors); and b) the well-documented contribution of both central command and muscle afferent feedback to effort perception. While we agree with the author that our data suggests that afferent feedback is the main contributor to the sensation of muscle fatigue, we disagree with the claim that our findings suggest that afferent feedback does not contribute to effort perception.
Naturally Long‐Lived Animal Models for the Study of Slow Aging and Longevity

Abstract: Judicious selection of new animal models for the study of basic aging processes must combine feasibility and good use of the comparative method with evidence of antiaging adaptations, like the ability to combat oxidative damage to cells and tissues. A number of vertebrate species already in use or being developed as new biomedical models lend themselves very well to laboratory studies of aging, including small birds, bats, and mole‐rats.
Strain Imaging: From Physiology to Practical Applications in Daily Practice

Non-Doppler, 2-dimensional strain imaging is a new echocardiographic technique for obtaining strain and strain rate measurements, which serves as a major advancement in understanding myocardial deformation. It analyzes motion in ultrasound imaging by tracking speckles in 2 dimensions. There are a lot of data emerging with multiple applications of strain imaging in the clinical practice of echocardiography. As incorporation of strain imaging in daily practice has been challenging, we intend to systematically highlight the top 10 applications of speckle-tracking echocardiography, which every cardiologist should be aware of: chemotherapy cardiotoxicity, left ventricular assessment, cardiac amyloidosis, hypertrophic obstructive cardiomyopathy, right ventricular dysfunction, valvular heart diseases (aortic stenosis and mitral regurgitation), cardiac sarcoidosis, athlete heart, left atrial assessment, and cardiac dyssynchrony.
Redistribution of Electrical Interconnections for Three-Dimensional Wafer-Level Packaging With Silicon Bumps

In this letter, an approach to the redistribution of electrical interconnections is investigated for potential application in 3-D wafer-level packaging. A cap wafer with silicon bumps and electrical feedthroughs is bonded together with a device wafer using wafer-level glass-frit bonding technology. During the bonding process, the mechanical bond is performed by glass-frit bonding to form hermetic packaging. Simultaneously, the silicon bumps provide close contact for the electrical feedthroughs on the cap wafer and the metal pads on the device wafer, on which a gold-aluminum eutectic is formed to achieve electrical interconnections between the cap wafer and the device wafer. Moreover, the silicon bumps provide a way to control well the height of the bonding materials. This process not only realizes a wafer-level hermetic sealing but also achieves the redistribution of electrical interconnections. Application of this approach for a high performance MEMS resonator is demonstrated, which illustrates the feasibility of this process.
Treatment Options to Elim- inate or Control Growth of Listeria monocytogenes on Raw Material and on Finished Product for the Smoked Fish Industry

MICHAEL L. JAHNCKE,1* ROBERT COLLETTE,2 DORIS HICKS,3 MARTIN WIEDMANN,4 VIRGINIA N. SCOTT,5 and KEN GALL6 1Virginia Seafood Agricultural Research and Extension Center, Virginia Sea Grant Program, Hampton, VA 23669, USA; 2National Fisheries Institute, Arlington, VA 22209, USA; 3University of Delaware Sea Grant College Program, Lewes, DE 19958, USA; 4Department of Food Science, Cornell University, Ithaca, NY 14853, USA; 5National Food Processors Association, Washington, D.C. 20005, USA; 6New York Sea Grant and Cornell Cooperative Extension, Stony Brook, NY 11794, USA