Miracle-dz/UniFAR-FTUs huggingface dataset:
Splice Cassette II of Na+,HCO3− Cotransporter NBCn1 (slc4a7) Interacts with Calcineurin A

Background: Signaling pathways linking artery contraction to increased acid extrusion and intracellular pH control have been unknown. Results: Calcineurin A interacts physically with Na+,HCO3− cotransporter NBCn1 and is required for activation of Na+,HCO3− cotransport during artery contraction. Conclusion: Ca2+-dependent activation of NBCn1 is mediated by calcineurin. Significance: Calcineurin-dependent activation of NBCn1 is critical for intracellular pH control during artery contraction. Activation of Na+,HCO3− cotransport in vascular smooth muscle cells (VSMCs) contributes to intracellular pH (pHi) control during artery contraction, but the signaling pathways involved have been unknown. We investigated whether physical and functional interactions between the Na+,HCO3− cotransporter NBCn1 (slc4a7) and the Ca2+/calmodulin-activated serine/threonine phosphatase calcineurin exist and play a role for pHi control in VSMCs. Using a yeast two-hybrid screen, we found that splice cassette II from the N terminus of NBCn1 interacts with calcineurin Aβ. When cassette II was truncated or mutated to disrupt the putative calcineurin binding motif PTVVIH, the interaction was abolished. Native NBCn1 and calcineurin Aβ co-immunoprecipitated from A7r5 rat VSMCs. A peptide (acetyl-DDIPTVVIH-amide), which mimics the putative calcineurin binding motif, inhibited the co-immunoprecipitation whereas a mutated peptide (acetyl-DDIATAVAA-amide) did not. Na+,HCO3− cotransport activity was investigated in VSMCs of mesenteric arteries after an NH4+ prepulse. During depolarization with 50 mm extracellular K+ to raise intracellular [Ca2+], Na+,HCO3− cotransport activity was inhibited 20–30% by calcineurin inhibitors (FK506 and cyclosporine A). FK506 did not affect Na+,HCO3− cotransport activity in VSMCs when cytosolic [Ca2+] was lowered by buffering, nor did it disrupt binding between NBCn1 and calcineurin Aβ. FK506 augmented the intracellular acidification of VSMCs during norepinephrine-induced artery contractions. No physical or functional interactions between calcineurin Aβ and the Na+/H+ exchanger NHE1 were observed in VSMCs. In conclusion, we demonstrate a physical interaction between calcineurin Aβ and cassette II of NBCn1. Intracellular Ca2+ activates Na+,HCO3− cotransport activity in VSMCs in a calcineurin-dependent manner which is important for protection against intracellular acidification.
A Lifespan Perspective on Cooperative Education Learning: A Grounded Theory.

This qualitative study sits at the intersection of two trends in vocational education. The first trend is a narrative approach to understanding cooperative education learning; the second is a movement away from career development theories toward the view that individuals use work experiences to help construct their lives. Both trends view learning as situated in social contexts and suggest narratives to discover the meanings individuals make of work experiences. A lifespan approach using interviews at or near retirement was employed to add a long developmental trajectory to the study of how cooperative education learning served one group of students across decades. A grounded theory of cooperative education learning was discovered through analysis of two sets of archived data. The theory explored the phenomenon via causal conditions, attributes, strategies, and consequences. The lifespan approach supports other literature in questioning some current practices in cooperative education and emphasizes some of the important contributions that co-op makes to long-term learning. (Asia-Pacific Journal of Cooperative Education, 2015, 16(4), 301-326)
Configuration and Dynamics of Xanthophylls in Light-harvesting Antennae of Higher Plants

Resonance Raman excitation spectroscopy combined with ultra low temperature absorption spectral analysis of the major xanthophylls of higher plants in isolated antenna and intact thylakoid membranes was used to identify carotenoid absorption regions and study their molecular configuration. The major electronic transitions of the light-harvesting complex of photosystem II (LHCIIb) xanthophylls have been identified for both the monomeric and trimeric states of the complex. One long wavelength state of lutein with a 0-0 transition at 510 nm was detected in LHCIIb trimers. The short wavelength 0-0 transitions of lutein and neoxanthin were located at 495 and 486 nm, respectively. In monomeric LHCIIb, both luteins absorb around 495 nm, but slight differences in their protein environments give rise to a broadening of this band. The resonance Raman spectra of violaxanthin and zeaxanthin in intact thylakoid membranes was determined. The broad 0-0 absorption transition for zeaxanthin was found to be located in the 503–511 nm region. Violaxanthin exhibited heterogeneity, having two populations with one absorbing at 497 nm (0-0), 460 nm (0-1), and 429 nm (0-2), and the other major pool absorbing at 488 nm (0-0), 452 nm (0-1), and 423 nm (0-2). The origin of this heterogeneity is discussed. The configuration of zeaxanthin and violaxanthin in thylakoid membranes was different from that of free pigments, and both xanthophylls (notably, zeaxanthin) were found to be well coordinated within the antenna proteins in vivo, arguing against the possibility of their free diffusion in the membrane and supporting our recent biochemical evidence of their association with intact oligomeric light-harvesting complexes (Ruban, A. V., Lee, P. J., Wentworth, M., Young, A. J., and Horton, P. (1999) J. Biol. Chem. 274, 10458–10465).
Cognitive and motor functional activity in non-demented community-dwelling essential tremor cases

Background Many investigators have observed mild cognitive deficits in essential tremor (ET), yet the functional significance of these deficits is unclear. Also, there are very few data in which functional activity in ET has been divided into cognitively based activities (remembering appointments) versus motor-based activities (writing cheques). Objective The authors (1) compared functional level in ET cases versus controls, assessing functional activities that are cognitively based and those that are dependent upon both motor and cognitive factors, and (2) determined whether lower mini mental status test scores in ET cases have a functional correlate. Methods In a population-based study of people ≥65 years in central Spain (NEDICES), a 37-item version of the Mini-Mental State Examination (37-MMSE) and an 11-item version of the Pfeffer Functional Activities Questionnaire (FAQ) were administered to non-demented ET cases and controls. Results The FAQ was 55.5% higher (ie, lower function) in 208 cases than 3616 controls (2.8±4.8 vs 1.8±4.2, p<0.001). Cases reported more difficulty (ie, higher FAQ scores) with FAQ items that were cognitive measures as well as FAQ items that were cognitive–motor in nature. In cases, a lower 37-MMSE was associated with more difficulty on both cognitively based and cognitive–motor-based FAQ items (p<0.001). Discussion In this large, population-based study, ET cases reported more functional difficulty than controls, and this functional difficulty was present in both cognitive and cognitive–motor domains. Lower cognitive test scores were associated with more reported functional difficulty, indicating that lower cognitive test scores in ET, rather than being inconsequential, have a clear clinical–functional correlate.
Solvation energies of amino acid side chains and backbone in a family of host-guest pentapeptides.

Octanol-to-water solvation free energies of acetyl amino amides (Ac-X-amides) [Fauchère, J.L. , & Pliska, V. (1983) Eur. J. Med. Chem. --Chim. Ther. 18,369] form the basis for computational comparisons of protein stabilities by means of the atomic solvation parameter formalism of Eisenberg and McLachlan [(1986) Nature 319, 199]. In order to explore this approach for more complex systems, we have determined by octanol-to-water partitioning the solvation energies of (1) the guest (X) side chains in the host-guest pentapeptides AcWL-X-LL, (2) the carboxy terminus of the pentapeptides, and (3) the peptide bonds of the homologous series of peptides AcWLm (m = 1-6). Solvation parameters were derived from the solvation energies using estimates of the solvent-accessible surface areas (ASA) obtained from hard-sphere Monte Carlo simulations. The measurements lead to a side chain solvation-energy scale for the pentapeptides and suggest the need for modifying the Asp, Glu, and Cys values of the "Fauchère-Pliska" solvation-energy scale fro the Ac-X-amides. We find that the unfavorable solvation energy of nonpolar residues can be calculated accurately by a solvation parameter of 22.8 +/- 0.8 cal/mol/A2, which agrees satisfactorily with the AC-X-amide data and thereby validates the Monte Carlo ASA results. Unlike the Ac-X-amide data, the apparent solvation energies of the uncharged polar residues are also largely unfavorable. This unexpected finding probably results, primarily, from differences in conformation and hydrogen bonding in octanol and buffer but may also be due to the additional flaking peptide bonds of the pentapeptides. The atomic solvation parameter (ASP) for the peptide bond is comparable to the ASP of the charged carboxy terminus which is an order of magnitude larger than the ASP of the uncharged polar side chains of the Ac-X-amides. The very large peptide bond ASP, -96 +/- 6 cal/mol/A2, profoundly affects the results of computational comparisons of protein stability which use ASPs derived from octanol-water partitioning data.
Mechatronic modeling and control of a lathe machine equipped with a MR damper for chatter suppression

Chatter vibration in machining operations is a limiting factor in enhancing metal cutting efficiency. This paper presents a novel semi-active intelligent control technique for chatter vibration supersession using tunable magnetorheological (MR) dampers. Structural dynamic characteristics of the machine tool (e.g., real and imaginary parts of the frequency response function) are the main parameters which specify the stability lobes diagram (SLD), i.e., the border between stable and unstable cutting conditions. In the present work, chatter reduction is achieved by altering these factors semi-actively, by means of a MR damper. First, a lumped model for MR damper is presented using modified Bouc-Wen model. Subsequently, integrated simulation software is developed for studying the vibration of a lathe machine equipped with a MR damper. An innovative real-time criterion is presented to recognize the chatter occurrence. A fuzzy controller is designed to calculate the voltage to be sent to MR damper at each instant to prevent chatter occurrence. The obtained results show that the proposed method has been successful in reducing the chatter conditions and improving the stability of turning operation with very low energy consumption.
Why are REITS Currently So Expensive

For the last several years, the price of listed real estate stocks has been unusually high relative to dividends. I explore whether low interest rates or low risk premia can account for the high valuation ratios and find that they cannot. Lower interest rates have been offset by rising risk premia to keep expected returns close to average. Instead, the market has priced in future income growth on commercial properties that is far above the growth rates seen in the data. High implied growth rates hold across traditional REIT sectors, but are less extreme for non-traditional REIT sectors. Income growth expectations are also less extreme for an index of international listed real estate. Investors who ignore the recent increase in interest rate risk that we document would need to hold lower, but still unusually large income growth expectations.
Efficacy of antiviral compounds in human herpesvirus-6-infected glial cells

The β-herpesvirus human herpesvirus-6 (HHV-6) is becoming increasingly recognized as an important pathogen in immunocompromised patients, particularly in post bone marrow transplant (BMT). Reactivation of latent HHV-6 resulting in encephalitis has been reported in BMT and stem cell transplant (SCT) patients. The development of HHV-6 encephalitis can be a fatal complication, the frequency of which is increasing likely due to improved diagnosis with quantitative polymerase chain reaction (PCR) of cerebrospinal fluid. There are currently no antiviral compounds approved for HHV-6, nor have any controlled clinical trials been conducted. The frequency and severity of HHV-6 encephalitis in both immunocompetent and immunocompromised patients necessitates studies on the usefulness of currently available anti-viral compounds. The authors compared the antiviral efficacy of four drugs currently used for cytomegalovirus (CMV) infection, a β-herpesvirus sharing homology with HHV-6. In HHV-6A— and HHV-6B—infected T cells, acyclovir, ganciclovir, foscarnet, and cidofovir exhibited antiviral activity consistent with that published in other studies. In HHV-6-infected human astrocytes (U251), however, only foscarnet and cidofovir exhibited antiviral activity and this effect was restricted to infection with HHV-6 variant A. In pathological brain sections from patients with neurological disorders such as multiple sclerosis and epilepsy, HHV-6 has been localized to glial cells. Determination of antiviral activity in human glial fibrillary acidic protein (GFAP)-positive astrocytes of currently used antiviral compounds is essential for potential treatment of HHV-6 and neurological disorders. Our data highlight the necessity for further study of antiviral compound in HHV-6—infected glial cells as well as the development of more selective compounds for HHV-6.
Current treatment paradigms in the management of lymphatic malformations

Lymphatic malformations (LMs) are benign abnormalities of the lymphatic system that can be significantly infiltrative and intimately involve critical structures of the head and neck, making their management difficult. Historically, LMs have been managed by surgical excision, but this treatment approach results in significant morbidity and a high recurrence rate secondary to subtotal resection. As an alternative to surgery a variety of drugs have been used as intralesional sclerosants and immunotherapeutics. These agents offer improved outcomes with lower morbidity as compared to surgery when targeted to macrocystic LMs. However intralesional therapy is not effective in the treatment of microcystic LMs. The development of treatments that are effective for all types of LMs will require further understanding of lymphangiogenesis and the pathogenesis of LMs. Laryngoscope, 2011
Transmembrane Topology of AgrB, the Protein Involved in the Post-translational Modification of AgrD in Staphylococcus aureus *

The accessory gene regulator (agr) ofStaphylococcus aureus is the central regulatory system that controls the gene expression for a large set of virulence factors. This global regulatory locus consists of two transcripts: RNAII and RNAIII. RNAII encodes four genes (agrA, B,C, and D) whose gene products assemble a quorum sensing system. RNAIII is the effector of the Agr response. Both theagrB and agrD genes are essential for the production of the autoinducing peptide, which functions as a signal for the quorum sensing system. In this study, we demonstrated the transmembrane nature of AgrB protein in S. aureus. A transmembrane topology model of AgrB was proposed based on AgrB-PhoA fusion analyses in Escherichia coli. Two hydrophilic regions with several highly conserved positively charged amino acid residues among various AgrBs were found to be located in the cytoplasmic membrane as suggested by PhoA-AgrB fusion studies. However, this finding is inconsistent with the putative transmembrane profile of AgrB by computer analysis. Furthermore, we detected an intermediate peptide of processed AgrD from S. aureus cells expressing AgrB and a 6 histidine-tagged AgrD. These results provide direct evidence that AgrB is involved in the proteolytic processing of AgrD. We speculate that AgrB is a novel protein with proteolytic enzyme activity and a transporter facilitating the export of the processed AgrD peptide.
ATF4/ATG5 Signaling in Hypothalamic Proopiomelanocortin Neurons Regulates Fat Mass via Affecting Energy Expenditure

Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. In this study, we showed that hypothalamic proopiomelanocortin (POMC) neuron–specific ATF4 knockout (PAKO) mice are lean and have higher energy expenditure. Furthermore, PAKO mice were resistant to high-fat diet–induced obesity, glucose intolerance, and leptin resistance. Moreover, the expression of autophagy protein 5 (ATG5) was increased or decreased by ATF4 knockdown or overexpression, respectively, and ATF4 inhibited the transcription of ATG5 by binding to the basic zipper-containing protein sites on its promoter. Importantly, mice with double knockout of ATF4 and ATG5 in POMC neurons gained more fat mass and reduced energy expenditure compared with PAKO mice under a high-fat diet. Finally, the effect of ATF4 deletion in POMC neurons was possibly mediated via enhanced ATG5-dependent autophagy and α-melanocyte–stimulating hormone production in the hypothalamus. Taken together, these results identify the beneficial role of hypothalamic ATF4/ATG5 axis in the regulation of energy expenditure, obesity, and obesity-related metabolic disorders, which suggests that ATF4/ATG5 axis in the hypothalamus may be a new potential therapeutic target for treating obesity and obesity-related metabolic diseases.
Applications of Real-Time Thermoregulatory Models to Occupational Heat Stress: Validation With Military and Civilian Field Studies

Abstract Yokota, M, Berglund, LG, Santee, WR, Buller, MJ, Karis, AJ, Roberts, WS, Cuddy, JS, Ruby, BC, and Hoyt, RW. Applications of real-time thermoregulatory models to occupational heat stress: Validation with military and civilian field studies. J Strength Cond Res 26(7): S37–S44, 2012. A real-time thermoregulatory model using noninvasive measurements as inputs was developed for predicting physiological responses of individuals working long hours. The purpose of the model is to reduce heat-related injuries and illness by predicting the physiological effects of thermal stress on individuals while working. The model was originally validated mainly by using data from controlled laboratory studies. This study expands the validation of the model with field data from 26 test volunteers, including US Marines, Australian soldiers, and US wildland fire fighters (WLFF). These data encompass a range of environmental conditions (air temperature: 19–30° C; relative humidity: 25–63%) and clothing (i.e., battle dress uniform, chemical-biological protective garment, WLFF protective gear), while performing diverse activities (e.g., marksmanship, marching, extinguishing fires, and digging). The predicted core temperatures (Tc), calculated using environmental, anthropometric, clothing, and heart rate measures collected in the field as model inputs, were compared with subjects' Tc collected with ingested telemetry temperature pills. Root mean standard deviation (RMSD) values, used for goodness of fit comparisons, indicated that overall, the model predictions were in close agreement with the measured values (grand mean of RMSD: 0.15–0.38° C). Although the field data showed more individual variability in the physiological data relative to more controlled laboratory studies, this study showed that the performance of the model was adequate.
School-based treatment for anxious african-american adolescents: a controlled pilot study.

OBJECTIVE To evaluate the feasibility and effectiveness of a school-based group cognitive-behavioral treatment (CBT) for anxiety disorders with African-American adolescents. METHOD Twelve adolescents (mean age = 15.6 years) with anxiety disorders were randomly assigned to CBT (n = 6) or a group attention-support control condition (AS-Control; n = 6). Both groups met for 10 sessions in the same high school. Key treatment ingredients in CBT involved exposure, relaxation, social skills, and cognitive restructuring. Key ingredients in AS-Control involved therapist and peer support. At pre- and posttreatment, diagnostic interviews were conducted, and adolescents completed self-report measures of anxiety. RESULTS At posttreatment and among those who attended more than one treatment session, 3/4 adolescents in CBT no longer met diagnostic criteria for their primary anxiety disorder, compared with 1/5 in AS-Control. Clinician ratings of impairment and self-report levels of overall anxiety were significantly lower at posttreatment in CBT compared with AS-Control. Teenagers in both groups reported lower levels of social anxiety from pre- to posttreatment. CONCLUSIONS Findings support the feasibility of implementing a manual-based CBT in an urban school setting. Responder rates among African-American adolescents were similar to those found in studies with white youths.
Prevalence of Potentially Distracting Noncare Activities and Their Effects on Vigilance, Workload, and Nonroutine Events during Anesthesia Care

Background: When workload is low, anesthesia providers may perform non–patient care activities of a clinical, educational, or personal nature. Data are limited on the incidence or impact of distractions on actual care. We examined the prevalence of self-initiated nonclinical distractions and their effects on anesthesia workload, vigilance, and the occurrence of nonroutine events. Methods: In 319 qualifying cases in an academic medical center using a Web-based electronic medical chart, a trained observer recorded video and performed behavioral task analysis. Participant workload and response to a vigilance (alarm) light were randomly measured. Postoperatively, participants were interviewed to elicit possible nonroutine events. Two anesthesiologists reviewed each event to evaluate their association with distractions. Results: At least one self-initiated distraction was observed in 171 cases (54%), largely during maintenance. Distractions accounted for 2% of case time and lasted 2.3 s (median). The most common distraction was personal internet use. Distractions were more common in longer cases but were not affected by case type or American Society of Anesthesiologists physical status. Workload ratings were significantly lower during distraction-containing case periods and vigilance latencies were significantly longer in cases without any distractions. Three distractions were temporally associated with, but did not cause, events. Conclusions: Both nurse anesthetists and residents performed potentially distracting tasks of a personal and/or educational nature in a majority of cases. Self-initiated distractions were rarely associated with events. This study suggests that anesthesia professionals using sound judgment can self-manage nonclinical activities. Future efforts should focus on eliminating more cognitively absorbing and less escapable distractions, as well as training in distraction management.