Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering of Solvent-Tolerant Pseudomonas putida S12 for Bioproduction of Phenol from Glucose

ABSTRACT Efficient bioconversion of glucose to phenol via the central metabolite tyrosine was achieved in the solvent-tolerant strain Pseudomonas putida S12. The tpl gene from Pantoea agglomerans, encoding tyrosine phenol lyase, was introduced into P. putida S12 to enable phenol production. Tyrosine availability was a bottleneck for efficient production. The production host was optimized by overexpressing the aroF-1 gene, which codes for the first enzyme in the tyrosine biosynthetic pathway, and by random mutagenesis procedures involving selection with the toxic antimetabolites m-fluoro-dl-phenylalanine and m-fluoro-l-tyrosine. High-throughput screening of analogue-resistant mutants obtained in this way yielded a P. putida S12 derivative capable of producing 1.5 mM phenol in a shake flask culture with a yield of 6.7% (mol/mol). In a fed-batch process, the productivity was limited by accumulation of 5 mM phenol in the medium. This toxicity was overcome by use of octanol as an extractant for phenol in a biphasic medium-octanol system. This approach resulted in accumulation of 58 mM phenol in the octanol phase, and there was a twofold increase in the overall production compared to a single-phase fed batch.
Introduction to the Special Issue Social Commerce: A Research Framework for Social Commerce

The increased popularity of social networking sites, such as Linkedln, Facebook, and Twitter, has opened opportunities for new business models for electronic commerce, often referred to as social commerce. Social commerce involves using Web 2.0 social media technologies and infrastructure to support online interactions and user contributions to assist in the acquisition of products and services. Social media technologies not only provide a new platform for entrepreneurs to innovate but also raise a variety of new issues for e-commerce researchers that require the development of new theories. This could become one of the most challenging research arenas in the coming decade. The purpose of this introduction is to present a framework that integrates several elements in social commerce research and to summarize the papers included in this special issue. The framework includes six key elements for classifying social commerce research: research theme, social media, commercial activities, underlying theories, outcomes, and research methods. The proposed framework is valuable in defining the scope and identifying potential research issues in social commerce. We also explain how the papers included in this special issue fit into the proposed research framework.
A novel GABAA receptor pharmacology: drugs interacting with the α+β‐ interface

GABAA receptors are ligand‐gated chloride channels composed of five subunits that can belong to different subunit classes. The existence of 19 different subunits gives rise to a multiplicity of GABAA receptor subtypes with distinct subunit composition; regional, cellular and subcellular distribution; and pharmacology. Most of these receptors are composed of two α, two β and one γ2 subunits. GABAA receptors are the site of action of a variety of pharmacologically and clinically important drugs, such as benzodiazepines, barbiturates, neuroactive steroids, anaesthetics and convulsants. Whereas GABA acts at the two extracellular β+α‐ interfaces of GABAA receptors, the allosteric modulatory benzodiazepines interact with the extracellular α+γ2‐ interface. In contrast, barbiturates, neuroactive steroids and anaesthetics seem to interact with solvent accessible pockets in the transmembrane domain. Several benzodiazepine site ligands have been identified that selectively interact with GABAA receptor subtypes containing α2βγ2, α3βγ2 or α5βγ2 subunits. This indicates that the different α subunit types present in these receptors convey sufficient structural differences to the benzodiazepine binding site to allow specific interaction with certain benzodiazepine site ligands. Recently, a novel drug binding site was identified at the α+β‐ interface. This binding site is homologous to the benzodiazepine binding site at the α+γ2‐ interface and is thus also strongly influenced by the type of α subunit present in the receptor. Drugs interacting with this binding site cannot directly activate but only allosterically modulate GABAA receptors. The possible importance of such drugs addressing a spectrum of receptor subtypes completely different from that of benzodiazepines is discussed.
Dermatoglyphic Variation in Spanish Basque Populations

The present study involves the evaluation of digital dermatoglyphic traits of 2185 unrelated individuals (1152 females and 1033 males) from 17 natural valleys of the four Basque provinces (Vizcaya, Guipúzcoa, Navarra, and Alava) in the Spanish Basque Country. Univariate intervalley and between-sex comparisons were carried out by means of chi-square contingency analysis for pattern types and by means of one-way analysis of variance for ridge counts. Multivariate intervalley comparison was carried out by means of correspondence analysis for pattern types and by principal component analysis for ridge counts. The results of this study are notable for the following findings: (1) in general, all variables are significantly heterogeneous among valley populations; (2) there was a greater differentiation among the valley populations than between sexes in one valley population; (3) affinities among the intervalley populations depend on the variables considered; (4) the valley populations from Vizcaya resemble those from the Pyrenees; (5) based on interprovince comparisons, the Vizcaya and Navarra samples are the closest; (6) in general, the valley samples from Alava are the worst clustered; (7) the universality of dermatoglyphic component structure fits better in males.
The impact of rest duration on work intensity and RPE during interval training.

PURPOSE To investigate the effect of rest duration on self-selected intensity, physiological responses, and RPE during a standardized, high-intensity interval training prescription. SUBJECTS Nine well-trained male runners (VO(2max) 71 +/- 4 mL.kg(-1). min(-1)) performed three treadmill interval training sessions running at constant 5% incline. Six 4-min work bouts with either 1-, 2-, or 4-min recovery periods were performed in each session. Sessions were prescribed as "high-intensity" workouts with the goal being to achieve the highest possible average running speed for the work intervals. Subjects regulated their work and rest intensity based on these instructions. In a fourth interval session, subjects self-selected recovery time in response to a fixed intensity. RESULTS Running velocity increased slightly (14.7 +/- 0.7 vs 14.4 +/- 0.8 km.h(-1), P = 0.02) when rest increased from 1 to 2 min, but showed no further increase with a 4-min rest (14.7 +/- 0.6 km.h(-1). Work VO(2) was slightly higher with a 2-min rest duration compared with 1 and 4 min (66.2 +/- 4.2 vs 65.1 +/- 4.2 and 64.9 +/- 4.7 mL.kg(-1). min(-1), P < 0.05). Peak blood lactate was similar (6.2 +/- 2.6, 6.8 +/- 2.9, 6.2 +/- 2.6 mmol.L(-1)) across conditions, whereas peak RPE was slightly lower during the 4-min rest condition (17.1 +/- 1.3, 17.7 +/- 1.5, 16.8 +/- 1.5, P < 0.05). With self-selected recovery time and no knowledge of elapsed time, the average rest duration was 118 +/- 23 s. CONCLUSIONS Under self-paced conditions, varying rest duration in a range of 1 to 4 min had limited impact on performance during repeated 4-min high-intensity exercise bouts. Approximately 120 s of active recovery may provide an appropriate balance between intracellular restitution and maintenance of high VO(2) on-kinetics.
Social media enabled human sensing for smart cities

Smart city initiatives rely on real-time measurements and data collected by a large number of heterogenous physical sensors deployed throughout a city. Physical sensors, however, are fraught with interoperability, dependability, management, and political challenges. Furthermore, these sensors are unable to sense the opinions and emotional reactions of citizens that invariably impact smart city initiatives. Yet everyday, millions of dwellers and visitors of a city share their observations, thoughts, feelings, and experiences, or in other words, their perceptions about their city through social media updates. This paper reasons why “human sensors”, namely, citizens that share information about their surroundings via social media can supplement, complement, or even replace the information measured by physical sensors. We present a methodology based on probabilistic language modeling to extract and visualize such perceptions that may be relevant to smart cities from social media updates. Using more than six million geo-tagged tweets collected over regions that feature widely varying geographical, social, cultural, and political characteristics and tweet densities, we illustrate the potential of social media enabled human sensing to address diverse smart city challenges.
Effects of Calcitriol Supplementation on the Hematological Parameters of Sleep Deprived Wistar Rats.

The present study investigates the hematologic effect of Calcitriol on rats undergoing sleep deprivation. Male Wistar rats were treated with Calcitriol 120 ng/kg and subjected to sleep deprivation for four successive days. Twenty four hour after last injection, animals were sacrificed and blood was collected for haematological analysis. A four-day sleep restriction caused a decline in total white cell count and increased mean cell hemoglobin and mean cell volume. Furthermore, red blood cell count, packed cell volume, hemoglobin concentration and mean cell hemoglobin concentration also declined in sleep deprived rats. Peripheral blood cell examination revealed that these effects were mild in rats treated with calcitriol. Our findings showed that a four-day paradoxical sleep restriction altered the biochemical integrity of erythrocytes. The observed immunosuppressive effects of sleep deprivation were reversed by exogenous vitamin D supplement, calcitriol. However, only the functional haemoglobin component of red cells was enhanced by a high dose of calcitriol which appears unbeneficial for other units of the erythroid-forming processes. It is therefore possible that the erythrocytic enhancing power of calcitriol is dose dependent and we suggest that lower doses (<120ng/kg) may be required to produce beneficial effects on erythropoiesis.
Randomised trial of an inhaled β2 agonist, inhaled corticosteroid and their combination in the treatment of asthma

BACKGROUND Although many asthmatic patients are treated with a combination of β2 agonist and corticosteroid inhalers, the clinical effects of combining the drugs are unknown. Studies on the early asthmatic response to allergen suggest that β2 agonists may reduce the benefit of inhaled corticosteroids. A study of the effects of combining the drugs on asthma control was undertaken. METHODS Sixty one subjects with mild to moderate asthma were randomised to a double blind crossover comparison of inhaled budesonide (200–400 μg twice daily), terbutaline (500–1000 μg four times daily), combined treatment, and placebo. Each treatment was given for six weeks following a four week washout period. Ipratropium was used for symptom relief. Treatments were ranked from worst (1) to best (4) based on need for oral steroid, mean morning peak flow, nocturnal awakening, ipratropium use, and asthma symptoms. Lung function and bronchial hyperresponsiveness were measured before and after each treatment. RESULTS Evaluable data for all four treatments were obtained from 47 subjects. The mean rank of each treatment was: placebo = 2.05; terbutaline = 2.13; budesonide = 2.48; combined treatment = 3.34. Combined treatment was ranked significantly better than any other treatment (p<0.01). Mean (95% CI) morning and evening peak flows were 14 (5 to 23) and 24 (15 to 34) l/min higher, respectively, during combined treatment than during budesonide, and 27 (17 to 37) and 15 (7 to 23) l/min higher than during terbutaline. Asthma symptoms tended to be least frequent during combined treatment but were not significantly different from budesonide alone. There was no significant difference between combined treatment and budesonide alone for lung function and bronchial hyperresponsiveness. CONCLUSIONS In this group of mild to moderate asthmatic subjects the combination of β2 agonist and corticosteroid gave better asthma control than either treatment alone. There was no evidence that regular β2 agonist treatment impaired the beneficial effect of inhaled corticosteroid.
Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones

A 4.6 kb Staphylococcus aureus DNA fragment containing DNA gyrase‐like genes (grlA and grlB) was cloned and sequenced. The proteins GrlA and GrlB exhibit more than 30% identity with E. coli DNA topoisomerase IV sub units and with the gyrase subunits from S. aureus and Escherichia coli. The combined E. coli cell extracts of GrlA and GrlB overproducing strains catalysed ATP‐dependent relaxation and decatenation specific to DNA topoisomerase IV. The temperature‐sensitive phenotype of Salmonella typhimurium parC and parE mutants was complemented by the S. aureus grlA and grlB genes, when the two genes were co‐expressed. These results show that GrlA and GrlB are the subunits of S. aureus DNA topoisomerase IV. The GyrA subunit of DNA gyrase has been previously defined as a primary target of quinolones based on genetic and biochemical experiments essentially carried out in E. coli. Single‐point mutations occurring in the‘quinolone resistance‐determining region’(QRDR) of GyrA were found in bacteria exhibiting quinolone resistance, the most common mutation being a substitution of Ser‐83 on the E. coli GyrA sequence. We analysed eight S. aureus fluoroquinolone‐resistant clinical isolates and observed that mutations in the QRDR of GyrA are not present in the low‐quinolone‐resistant isolates. In contrast, Ser‐80 of GrlA, which corresponds to Ser‐83 of E. coli GyrA, is substituted to Phe or Tyr in both high‐ and low‐quinolone‐resistant isolates. We propose that DNA topoisomerase IV is a primary target of fluoroquinolones in S. aureus.
Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis

Editors' Note: In WriteClick this week, Dr. Jellinger reports an analysis of a 50-year series of 604 patients clinically diagnosed with Parkinson disease and later confirmed via autopsy, and finds accuracy results similar to those in “Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis. ” Authors Logroscino et al. respond, reporting new diagnostic criteria that may improve accuracy and emphasizing the emerging importance of biomarkers. Dr. Topaloglu and authors Gloss et al. discuss the dosage guidelines for corticosteroid treatment in Duchenne muscular dystrophy, potential side effects, and future therapies. —Megan Alcauskas, MD, and Robert C. Griggs, MD In a meta-analysis …
Dehydroepiandrosterone Alters Zucker Rat Soleus and Cardiac Muscle Lipid Profiles

High levels of serum free fatty acids (FFA) and lower proportions of polyunsaturated (PU) FAs, specifically arachidonic acid (AA), are common in obesity, insulin resistance (IR), and type 2 diabetes mellitus. Dehydrepiandrosterone (DHEA) decreases body fat content, dietary fat consumption, and insulin levels in obese Zucker rats (ZR), a genetic model of human youth onset obesity and type 2 diabetes. This study was conducted to investigate DHEA's effects on lean and obese ZR serum FFA levels and total lipid (TL) FA profiles in heart and soleus muscle. We postulated that DHEA alters serum FFA levels and tissue TL FA profiles of obese ZR so that they resemble the levels and profiles of lean ZR. If so, DHEA may directly or indirectly alter tissue lipids, FFA flux, and perhaps lower IR in obese ZR. Lean and obese male ZR were divided into six groups with 10 animals in each: obese ad libitum control, obese pair-fed, obese DHEA, lean ad libitum control, lean pair-fed, and lean DHEA. All animals had ad libitum access to a diet whose calories were 50% fat, 30% carbohydrate, and 20% protein. Only the diets of the DHEA treatment groups were supplemented with 0.6% DHEA. Pair-fed groups were given the average number of calories per day consumed by their corresponding DHEA group, and ad libitum groups had 24-h access to the DHEA-free diet. Serum FFA levels and heart and soleus TL FA profiles were measured. Serum FFA levels were higher in obese (~1 mmol/L) compared to lean (~0.6 mmol/L) ZR, regardless of group. In hearts, monounsaturated (MU) FA were greater and PU FA were proportionally lower in obese compared to the lean rats. In soleus, saturated and MU FA were greater and PU FA were proportionally lower in the obese compared to the lean rats. DHEA groups displayed significantly increased proportions of TL AA and decreased oleic acid in both muscle types. Mechanisms by which DHEA alters TL FA profiles are a reflection of changes occurring within specific lipid fractions such as FFA, phospholipid, and triglyceride. This study provides initial insights into DHEA's lipid altering effects.
Curcumin ameliorates severe influenza pneumonia via attenuating lung injury and regulating macrophage cytokines production

Curcumin, an active phenolic agent extract from the Curcuma longa, exhibits excellent anti‐cancer, anti‐inflammation, and neuroprotective effects. We aimed to investigate the anti‐influenza role of curcumin in vitro and in vivo. The effect of curcumin on replication of influenza A virus (IAV) was examined in human lung cancer cell line A549, as well as in a mouse model. Curcumin could inhibit IAV in vitro and alleviate the severity of the disease in the mouse after infection with IAV. The results also indicated that curcumin could trigger expression of Heme oxygenase‐1 in vivo and attenuate IAV‐induced injury to the lung tissue. Furthermore, curcumin could regulate immune response following IAV infection through inhibiting production of local inflammatory cytokines. In addition, curcumin was found to inhibit NF‐κB signalling in macrophages, as well as the subsequent production of cytokines/chemokines responding to IAV infection, by enhancing IκBα and AMPK. Our current study supports the potential of curcumin as a promising treatment against IAV infection, whose effect may be mediated by regulating immune response to prevent injury to the lung tissue.
Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism.

Thyroid hormone effects on myocardial gene expression have been well defined in animal models, but their relationship to the pathogenesis of cardiac dysfunction in hypothyroid humans has been uncertain. We evaluated a profoundly hypothyroid young man with dilated cardiomyopathy. Before and during 9 months of thyroxine therapy, serial assessment of myocardial performance documented substantial improvements in the left ventricular ejection fraction (16-37%), left ventricular end-diastolic diameter (7.8-5.9 cm), and cardiac index (1.4-2.7 liters.min-1.m-2). Steady-state levels of mRNAs encoding selected cardiac proteins were measured in biopsy samples obtained before and after thyroxine replacement. In comparison with myocardium from nonfailing control hearts, this patient's pretreatment alpha-myosin heavy-chain mRNA level was substantially lower, the atrial natriuretic factor mRNA level was markedly elevated, and the phospholamban mRNA level was decreased. All of these derangements were reversed 9 months after restoration of euthyroidism. These observations in an unusual patient with profound myxedema and cardiac dilatation permit correlation between the reversible changes in myocardial function and steady-state mRNA levels in a cardiomyopathy. They suggest that alterations in gene expression in the dilated myopathic heart may be correctable when a treatable cause is identified.
Left-right asymmetry in the buildup of echo suppression in normal-hearing adults.

Echo threshold is that critical delay of a logging signal (the echo) at which the echo is "suppressed"--i.e., at which one rather than two events is perceived. It has recently been shown that echo threshold increases in most subjects when they are exposed to a train of redundant information prior to the test stimulus presentation--that is, there is buildup of echo suppression in the presence of the preceding train [Clifton et al., J. Acoust. Soc. Am. 95, 1525-1533 (1994)]. The present investigation measured echo threshold in 25 normal-hearing adult subjects, both for isolated (baseline) test stimuli and for test stimuli preceded by a redundant train of stimuli (buildup conditions). The test stimulus was a 4-microsecond wideband noise burst pair, in which the lead burst was presented from either the left or right side (from near -45 degrees or or near (+)45 degrees in different runs), and the lag burst was presented from the opposite side. Echo delay was varied adaptively, and the subject's task was to indicate on each trial which of two alternative positions (separated by 20 degrees) the lag sources was presented from. Average echo threshold in the baseline condition was 11.2 microseconds (in agreement with previous results) and did not depend on whether the lead burst was on the subject's left or right side. Average echo threshold in the buildup conditions was significantly elevated. Interestingly, there was a significantly greater buildup effect when the lead stimulus came from the subject's right side (average echo threshold: 24.4 microseconds) than when it came from the left side (average: 18.8 microseconds). This result agrees with informal observations made by Clifton and Freyman [Percept. Psychophys. 46, 139-145 (1989)] and suggests that there is more effective suppression of echo information when the lead stimulus originates from the right side (i.e., the side contralateral to the typically dominant hemisphere) that when it originates from the left side. The distribution of the magnitude of buildup effects across subjects (i.e., echo threshold in the presence of the train minus baseline echo threshold) was unimodal and symmetric, both for lag source on left (mean: 14.1 microseconds) and for lag source on right (mean: 6.7 microseconds). These results are discussed in relation to other hearing asymmetries that have been reported.