Miracle-dz/UniFAR-FTUs huggingface dataset:
Association with the Plasma Membrane Is Sufficient for Potentiating Catalytic Activity of Regulators of G Protein Signaling (RGS) Proteins of the R7 Subfamily*

Regulators of G protein Signaling (RGS) promote deactivation of heterotrimeric G proteins thus controlling the magnitude and kinetics of responses mediated by G protein-coupled receptors (GPCR). In the nervous system, RGS7 and RGS9–2 play essential role in vision, reward processing, and movement control. Both RGS7 and RGS9–2 belong to the R7 subfamily of RGS proteins that form macromolecular complexes with R7-binding protein (R7BP). R7BP targets RGS proteins to the plasma membrane and augments their GTPase-accelerating protein (GAP) activity, ultimately accelerating deactivation of G protein signaling. However, it remains unclear if R7BP serves exclusively as a membrane anchoring subunit or further modulates RGS proteins to increase their GAP activity. To directly answer this question, we utilized a rapidly reversible chemically induced protein dimerization system that enabled us to control RGS localization independent from R7BP in living cells. To monitor kinetics of Gα deactivation, we coupled this strategy with measuring changes in the GAP activity by bioluminescence resonance energy transfer-based assay in a cellular system containing μ-opioid receptor. This approach was used to correlate changes in RGS localization and activity in the presence or absence of R7BP. Strikingly, we observed that RGS activity is augmented by membrane recruitment, in an orientation independent manner with no additional contributions provided by R7BP. These findings argue that the association of R7 RGS proteins with the membrane environment provides a major direct contribution to modulation of their GAP activity.
A P&Q based synchronization technique for Bi-directional IPT pick-ups

Bi-directional Inductive Power Transfer (IPT) systems essentially require some form of synchronization between loads (pick-ups) and the main or primary power source. This paper presents a novel technique that can be used to synchronize pickups of a bi-directional IPT system with the primary converter (source). The proposed technique monitors the real (P) and reactive (Q) power generated by the corresponding pickup converter and conditioning it to follow a predetermined value, therefore forcing the pickup converter to operate in synchronization with the primary converter. A detailed analysis of the proposed technique is presented to verify its stability under different operating conditions. The viability of the technique, which is applicable to both single and multiple pick-up bi-directional IPT systems, is demonstrated through simulations of a 1.5 kW system.
A Wideband Low-Distortion CMOS Current Driver for Tissue Impedance Analysis

Bioimpedance measurements are performed in a variety of medical applications including cancer detection in tissue. Such applications require wideband (typically 1 MHz) accurate ac current drivers with high output impedance and low distortion. This paper presents an integrated current driver that fulfills these requirements. The circuit uses negative feedback to accurately set the output current amplitude into the load. It was fabricated in a 0.35-μm complementary metal-oxide-semiconductor (CMOS) process technology, occupies a core area of 0.4 mm2 , and operates from ±2.5-V power supplies. For a maximum output current of 1 mAp-p, the measured total harmonic distortion is below 0.1%, and the variability of the output current with respect to the load is below 0.5% up to 800 kHz increasing to 0.86% at 1 MHz. The current driver was tested for the detection of cancer sites from postoperative human colon specimens. The circuit is intended for use in active electrode applications.
Binding of intimin from enteropathogenic Escherichia coli to Tir and to host cells

Enteropathogenic Escherichia coli (EPEC) induce characteristic attaching and effacing (A/E) lesions on epithelial cells. This event is mediated, in part, by binding of the bacterial outer membrane protein, intimin, to a second EPEC protein, Tir (translocated intimin receptor), which is exported by the bacteria and integrated into the host cell plasma membrane. In this study, we have localized the intimin‐binding domain of Tir to a central 107‐amino‐acid region, designated Tir‐M. We provide evidence that both the amino‐ and carboxy‐termini of Tir are located within the host cell. In addition, using immunogold labelling electron microscopy, we have confirmed that intimin can bind independently to host cells even in the absence of Tir. This Tir‐independent interaction and the ability of EPEC to induce A/E lesions requires an intact lectin‐like module residing at the carboxy‐terminus of the intimin polypeptide. Using the yeast two‐hybrid system and gel overlays, we show that intimin can bind both Tir and Tir‐M even when the lectin‐like domain is disrupted. These data provide strong evidence that intimin interacts not only with Tir but also in a lectin‐like manner with a host cell intimin receptor.
arbon dioxide and water fluxes from switchgrass managed for bioenergy roduction

Switchgrass (Panicum virgatum L.) is an important bioenergy crop with the potential to provide a reliable supply of renewable energy while also sequestering C in the soil. The purpose of this study was to quantify CO2 fluxes during the establishment and early production years of a young switchgrass stand in the northeastern USA. Switchgrass was sown in June 2004 and daily CO2 fluxes were measured for four years. Gross primary productivity (GPP) varied little among years, but ecosystem respiration (Re) decreased over
Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality.

CONTEXT Adequate adrenal function is pivotal to survive meningococcal sepsis. OBJECTIVES The objective of the study was to evaluate adrenocortical function in meningococcal disease. DESIGN This was an observational cohort study. SETTING The study was conducted at a university-affiliated pediatric intensive care unit. PATIENTS Sixty children with meningococcal sepsis or septic shock participated in the study. MAIN OUTCOME MEASURES The differences in adrenal function between nonsurvivors (n = 8), shock survivors (n = 43), and sepsis survivors (n = 9) on pediatric intensive care unit admission were measured. RESULTS Nonsurvivors had significantly lower median cortisol to ACTH ratio than shock survivors and sepsis survivors. Because cortisol binding globulin and albumin levels did not significantly differ among the groups, bioavailable cortisol levels were also significantly lower in nonsurvivors than sepsis survivors. Nonsurvivors had significantly lower cortisol to 11-deoxycortisol ratios but not lower 11-deoxycortisol to 17-hydroxyprogesterone ratios than survivors. Using multiple regression analysis, decreased cortisol to ACTH ratio was significantly related to higher IL-6 levels and intubation with etomidate (one single bolus), whereas decreased cortisol to 11-deoxycortisol ratio was significantly related only to intubation with etomidate. Aldosterone levels tended to be higher in nonsurvivors than shock survivors, whereas plasma renin activity did not significantly differ. CONCLUSIONS Our study shows that the most severely ill children with septic shock had signs of adrenal insufficiency. Bioavailable cortisol levels were not more informative on adrenal function than total cortisol levels. Besides disease severity, one single bolus of etomidate during intubation was related to decreased adrenal function and 11beta-hydroxylase activity. Decreased adrenal function was not related to decreased 21-hydroxylase activity. Based on our results, it seems of vital importance to take considerable caution using etomidate and consider combining its administration with glucocorticoids during intubation of children with septic shock.
Transcriptional Heat Shock Response in the Smallest Known Self-Replicating Cell, Mycoplasma genitalium

ABSTRACT Mycoplasma genitalium is a human bacterial pathogen linked to urethritis and other sexually transmitted diseases as well as respiratory and joint pathologies. Though its complete genome sequence is available, little is understood about the regulation of gene expression in this smallest known, self-replicating cell, as its genome lacks orthologues for most of the conventional bacterial regulators. Still, the transcriptional repressor HrcA (heat regulation at CIRCE [controlling inverted repeat of chaperone expression]) is predicted in the M. genitalium genome as well as three copies of its corresponding regulatory sequence CIRCE. We investigated the transcriptional response of M. genitalium to elevated temperatures and detected the differential induction of four hsp genes. Three of the up-regulated genes, which encode DnaK, ClpB, and Lon, possess CIRCE within their promoter regions, suggesting that the HrcA-CIRCE regulatory mechanism is functional. Additionally, one of three DnaJ-encoding genes was up-regulated, even though no known regulatory sequences were found in the promoter region. Transcript levels returned to control values after 1 h of incubation at 37°C, reinforcing the transient nature of the heat shock transcriptional response. Interestingly, neither of the groESL operon genes, which encode the GroEL chaperone and its cochaperone GroES, responded to heat shock. These data suggest that M. genitalium selectively regulates a limited number of genes in response to heat shock.
Rootstock Sub-Optimal Temperature Tolerance Determines Transcriptomic Responses after Long-Term Root Cooling in Rootstocks and Scions of Grafted Tomato Plants

Grafting of elite cultivars onto tolerant rootstocks is an advanced strategy to increase tomato tolerance to sub-optimal temperature. However, a detailed understanding of adaptive mechanisms to sub-optimal temperature in rootstocks and scions of grafting combinations on a physiological and molecular level is lacking. Here, the commercial cultivar Kommeet was grafted either onto ‘Moneymaker’ (sensitive) or onto the line accession LA 1777 of Solanum habrochaites (tolerant). Grafted plants were grown in NFT-system at either optimal (25°C) or sub-optimal (15°C) temperatures in the root environment with optimal air temperature (25°C) for 22 days. Grafting onto the differently tolerant rootstocks caused differences in shoot fresh and dry weight, total leaf area and dry matter content of roots, in stomatal conductance and intercellular CO2 and guaiacol peroxidase activity but not in net photosynthesis, sugar, starch and amino acid content, lipid peroxidation and antioxidant enzyme activity. In leaves, comparative transcriptome analysis identified 361 differentially expressed genes (DEG) responding to sub-optimal root temperature when ‘Kommeet’ was grafted onto the sensitive but no when grafted onto the tolerant rootstock. 1509 and 2036 DEG responding to sub-optimal temperature were identified in LA 1777 and ‘Moneymaker’ rootstocks, respectively. In tolerant rootstocks down-regulated genes were enriched in main stress-responsive functional categories and up-regulated genes in cellulose synthesis suggesting that cellulose synthesis may be one of the main adaptation mechanisms to long-term sub-optimal temperature. Down-regulated genes of the sensitive rootstock showed a similar response, but functional categories of up-regulated genes pointed to induced stress responses. Rootstocks of the sensitive cultivar Moneymaker showed in addition an enrichment of up-regulated genes in the functional categories fatty acid desaturation, phenylpropanoids, biotic stress, cytochrome P450 and protein degradation, indicating that the sensitive cultivar showed more transcriptional adaptation to low temperature than the tolerant cultivar that did not show these changes. Mainly defense-related genes were highly differentially expressed between the tolerant and sensitive rootstock genotypes under sub-optimal temperature in the root environment. These results provide new insights into the molecular mechanisms of long-term sub-optimal temperature tolerance of tomato.
Microscopic Multilingual Matrix Test Predictions Using an ASR-Based Speech Recognition Model

In an attempt to predict the outcomes of matrix sentence tests in different languages and various noise conditions for native listeners, the simulation framework for auditory discrimination experiments (FADE) and the extended Speech Intelligibility Index (eSII) is employed. FADE uses an automatic speech recognition system to simulate recognition experiments and reports the highest achievable performance as the outcome, which showed good predictions for the German matrix test in noise. The eSII is based on the short-time analysis of weighted signalto-noise ratios in different frequency bands. In contrast to many other approaches, including the eSII, FADE uses no empirical reference. In this work, the FADE approach is evaluated for predictions of the German, Polish, Russian, and Spanish matrix test in stationary and fluctuating noise conditions. The FADEbased predictions yield a high correlation (Pearsons R = 0.94) with the empirical data and a root-mean-square (RMS) prediction error of 1.9 dB outperforming the eSII-based predictions (R = 0.78, RMS = 4.2 dB). FADE can also predict the data of subgroups with only stationary or only fluctuating noises, while the eSII cannot. The FADE-based predictions seem to generalize over different languages and noise conditions.
Transcriptional Repression and RNA Silencing Act Synergistically To Demonstrate the Function of the Eleventh Component of the Vaccinia Virus Entry-Fusion Complex

ABSTRACT Poxviruses have an elaborate system for infecting cells comprising several proteins for attachment and a larger number dedicated to membrane fusion and entry. Thus far, 11 proteins have been identified as components of the vaccinia virus (VACV) entry-fusion complex (EFC), and 10 of these proteins have been shown to be required for entry. J5, the remaining functionally uncharacterized component of the complex, is conserved in all poxviruses, has a predicted C-terminal transmembrane domain, and is an N-terminally truncated paralog of two other EFC proteins. To determine the role of J5, we constructed a mutant that inducibly regulates J5 transcription. Although the virus yield was reduced only about 80% without inducer, the inability to isolate a J5 deletion mutant suggested an essential function. To enhance stringency, we employed RNA silencing alone and together with transcriptional repression of the inducible mutant. The yield of infectious virus was reduced 4- to 5-fold by repression, 2-fold by silencing, and 60-fold by the combination of the two. Virus particles made under the latter conditions appeared to contain a full complement of proteins excluding J5 but had very low infectivity. Further studies indicated that after binding to cells, J5-deficient virions had a defect in core entry and an inability to induce syncytium formation. In addition, we confirmed that J5 is associated with the EFC by affinity purification. These data indicate that J5 is a functional component of the EFC and highlights the advantage of combining transcriptional repression and RNA silencing for stringent reduction of gene expression.
Postoperative Cognitive Dysfunction Is Independent of Type of Surgery and Anesthetic

BACKGROUND: Postoperative cognitive dysfunction (POCD) has been documented after cardiac and noncardiac surgery. The type of surgery and anesthetic has been assumed to be associated with the incidence but there are few prospective data comparing the incidence after different procedures. In this study, we sought to determine the association of the type of surgical procedure and anesthesia on the incidence of POCD after procedures involving light sedation, general anesthesia for noncardiac surgery, and general anesthesia for cardiac surgery involving cardiopulmonary bypass. METHODS: Eight neuropsychological tests were administered at baseline and at 7 days and 3 months postoperatively to subjects from 3 procedure groups and a nonoperative control group. Reliable change index was used to calculate POCD. The study sample consisted of subjects involved in 3 separate trials investigating coronary angiography (CA) (percutaneous diagnostic procedure) under sedation, major noncardiac surgery (total hip joint replacement [THJR] surgery) under general anesthesia, and coronary artery bypass graft (CABG) surgery under general anesthesia. RESULTS: Data were collected from 644 patients in the patient groups and 34 subjects in the control group. Neuropsychological results were available for POCD at day 7 for THJR surgery (n = 162) and CABG surgery (n = 281). The incidence of POCD at day 7 was 17% for THJR surgery and 43% for CABG surgery (adjusted odds ratio = 0.2, 95% confidence interval [CI]: 0.1, 0.4; P < 0.01). At 3 months, the incidence of POCD for all groups combined (n = 636) was 17% (21% for CA under sedation, 16% for THJR surgery, and 16% for CABG surgery). The mean (95% CI) for the difference in proportions of POCD among groups was 0.00 (−0.07, 0.07) (P = 0.91) for CABG versus THJR; −0.05 (−0.12, 0.03) (P = 0.21) for CABG versus CA; and −0.05 (−0.13, 0.03) (P = 0.24) for THJR versus CA. There were no significant differences among groups (adjusted odds ratio = 1.21, 95% CI: 0.94, 1.55; P = 0.13). CONCLUSIONS: The incidence of POCD in old and elderly patients at day 7 was higher after CABG surgery than THJR surgery, but POCD at 3 months was independent of the nature or the type of procedure or anesthetic when comparing CA, THJR, and CABG surgery groups. Cardiovascular risk factors were not predictive of POCD after any procedure.
Temperature-induced responses of xylem structure of Larix sibirica (Pinaceae) from the Russian Altay.

PREMISE OF THE STUDY Xylem structure determines the hydraulic and mechanical properties of a stem, and its plasticity is fundamental for maintaining tree performance under changing conditions. Unveiling the mechanism and the range of xylem adjustment is thus necessary to anticipate climate change impacts on vegetation. METHODS To understand the mechanistic process and the functional impact of xylem responses to warming in a cold-limited environment, we investigated the relationship between temperature and tracheid anatomy along a 312-yr tree-ring chronology of Larix sibirica trees from the Altay Mountains in Russia. KEY RESULTS Climate-growth analyses indicated that warming favors wider earlywood cell lumen, thicker latewood walls, denser maximum latewood, and wider rings. The temperature signal of the latewood was stronger (r > 0.7) and covered a longer and more stable period (from June to August) than that of earlywood and tree-ring width. Long-term analyses indicated a diverging trend between lumen and cell wall of early- and latewood. CONCLUSIONS Xylem anatomy appears to respond to warming temperatures. A warmer early-growing season raises water conduction capacity by increasing the number and size of earlywood tracheids. The higher-performing earlywood tracheids promote more carbon fixation of the latewood cells by incrementing the rate of assimilation when summer conditions are favorable for growth. The diverging long-term variation of lumen and cell wall in earlywood vs. latewood suggests that xylem adjustments in latewood increase mechanical integrity and support increasing tree size under the ameliorated growing conditions.
PARALLEL EVOLUTION OF LAKE‐STREAM PAIRS OF THREESPINE STICKLEBACKS (GASTEROSTEUS) INFERRED FROM MITOCHONDRIAL DNA VARIATION

Three drainage systems in British Columbia, Canada, contain divergent parapatric lake‐stream pairs of threespine sticklebacks (Gasterosteus aculeatus): Drizzle and Mayer Lakes on Graham Island, Queen Charlotte Islands, and Misty Lake on northeastern Vancouver Island. Ecological and morphological differences between members of all three lake‐stream pairs are strikingly similar; lake fish are melanistic and slim bodied with smaller mouths and more gill rakers than the mottled‐brown and robust‐bodied stream sticklebacks. We estimated the level of genetic divergence between lake and stream fish in Misty Lake and tested hypotheses of single versus multiple origins of the pairs by assaying mitochondrial DNA (mtDNA) restriction site variation in samples from the three lake systems. MtDNA analysis revealed the existence of two highly divergent lineages differing by 2.7% in sequence. One lineage predominated in Misty stream fish (73%), whereas the other lineage predominated in Misty Lake samples (96%). Comparable forms (lake or stream) in the different lakes did not cluster together in terms of mtDNA nucleotide divergence, suggesting that the pairs have had independent origins. We concluded that: (1) divergent mtDNA lineages in North Pacific sticklebacks stem from historical isolation in the two major glacial refugia proposed for the North Pacific (Beringia and Cascadia); (2) the stream and lake pair in Misty Lake are distinct gene pools; (3) the divergence between parapatric lake and stream Gasterosteus represents parallel evolution having occurred at least twice in the North Pacific; and (4) different scales of evolutionary divergence exist in North Pacific Gasterosteus, that is, a relatively ancient divergence of mtDNA clades as well as recent (i.e., postglacial) divergence of ecotypes within major clades.
Effectiveness of routine urine analysis of patient attending rural health centers in Abbottabad.

BACKGROUND Renal diseases may be discovered accidentally during routine urinalysis. This study was done to see the significance of urinalysis and study the magnitude of abnormal urinalysis in patients with no symptoms of renal disease. METHODS From 15th February to 16th March 2005, a total of 1000 samples of urine were collected from the patients attending three rural health centers of Abbottabad. Dipstick Method was used for urinalysis. RESULTS there were 600 males and 400 female patients. The age ranged from 1 to 55 years. Proteinuria was present in 2.3%, hematuria in 4.8% patients, pyuria in 10.2% and glycosuria in 2% patients. CONCLUSION In our setup routine urine analysis should be performed in all patients to identify the presence of unrecognized renal diseases which may benefit from simple therapeutic measures.