Miracle-dz/UniFAR-FTUs huggingface dataset:
Autophosphorylation-dependent activation of a calcium-dependent protein kinase from groundnut

Ca2+-dependent protein kinases (CDPKs) containing a calmodulin-like domain integrated in their primary sequence are present primarily in plants. A member of this family was characterized from the groundnut (Arachis hypogea) plant and called GnCDPK (M. DasGupta [1994] Plant Physiol 104: 961-969). GnCDPK specifically uses the myosin light chain synthetic peptide (MLCpep), which is the phosphate-accepting domain of smooth muscle myosin light chains (KKRPQRATSNVFS), as an exogenous substrate under in vitro experimental conditions. In this report we show that GnCDPK undergoes intramolecular autophosphorylation. This self-phosphorylation occurs in threonine residues in a Ca2+-dependent (K0.5 = 0.5 &mgr;M) and calmodulin-independent manner. The kinase activity toward MLCpep and its sensitivity to Ca2+ were unaffected by prior autophosphorylation when measured under saturating ATP concentrations. The role of autophosphorylation in the exogenous substrate MLCpep phosphorylation reaction was reinvestigated at low ATP concentrations. A pronounced lag time of 1 to 2 min, followed by a linear increase of activity for 7.5 min, was seen in the initial rate of MLCpep phosphorylation under such suboptimal conditions. Prior autophosphorylation completely abolished this lag phase, and a sharp rise of exogenous substrate phosphorylation was seen from the 1st min. Our results suggest that autophosphorylation is a prerequisite for the activation of GnCDPK.
Air pollution and your brain: what do you need to know right now

Research links air pollution mostly to respiratory and cardiovascular disease. The effects of air pollution on the central nervous system (CNS) are not broadly recognized. Urban outdoor pollution is a global public health problem particularly severe in megacities and in underdeveloped countries, but large and small cities in the United States and the United Kingom are not spared. Fine and ultrafine particulate matter (UFPM) defined by aerodynamic diameter (<2.5-μm fine particles, PM2.5, and <100-nm UFPM) pose a special interest for the brain effects given the capability of very small particles to reach the brain. In adults, ambient pollution is associated to stroke and depression, whereas the emerging picture in children show significant systemic inflammation, immunodysregulation at systemic, intratechal and brain levels, neuroinflammation and brain oxidative stress, along with the main hallmarks of Alzheimer and Parkinson’s diseases: hyperphosphorilated tau, amyloid plaques and misfolded α-synuclein. Animal models exposed to particulate matter components show markers of both neuroinflammation and neurodegeneration. Epidemiological, cognitive, behavioral and mechanistic studies into the association between air pollution exposures and the development of CNS damage particularly in children are of pressing importance for public health and quality of life. Primary health providers have to include a complete prenatal and postnatal environmental and occupational history to indoor and outdoor toxic hazards and measures should be taken to prevent or reduce further exposures.
Citius, Altius, Fortius: beneficial effects of resistance training for young athletes: Narrative review

The motto of the Olympic Games is Citius, Altius, Fortius which is Latin for ‘Faster, Higher, Stronger’. It is a clarion call to all competitors, including the youngest, to engage in training strategies that prepare athletes to be the best in the world. Existing research indicates that various forms of resistance training can elicit performance improvements in young athletes. Stronger young athletes will be better prepared to learn complex movements, master sport tactics, and sustain the demands of training and competition. An integrative training programme grounded in resistance training and motor skill development can optimise a young athlete's potential to maximise their athletic and sporting performance, while reducing the risk of a sports-related injury. Resistance training may be especially important for modern-day young athletes who are more likely to specialise in one sport at an early age at the expense of enhancing general physical fitness and learning diversified sport skills. Structured interventions that include qualified instruction; targeted movement practice; and strength and conditioning activities that are developmentally appropriate, progressive and technique driven are needed to attain a level of athleticism that is consistent with the Olympic motto.
κ-Conotoxin Pviia Is a Peptide Inhibiting theShaker K+ Channel*

κ-Conotoxin Pviia(κ-Pviia), a 27-amino acid toxin from Conus purpurascens venom that inhibits the Shaker potassium channel, was chemically synthesized in a biologically active form. The disulfide connectivity of the peptide was determined. κ-Conotoxin Pviia has the following structure. This is the first Conus peptide known to target K+channels. Although the Shaker K+ channel is sensitive to κ-Pviia, the rat brain Kv1.1 subtype is resistant. Chimeras between Shaker and the Kv1.1 K+ channels were constructed and expressed inXenopus oocytes. Only channels containing the putative pore-forming region between the fifth and sixth transmembrane domains of Shaker retained toxin sensitivity, indicating that the toxin target site is in this region of the channel. Evidence is presented that κ-Pviia interacts with the external tetraethyl-ammonium binding site on the Shaker channel. Although both κ-Pviia and charybdotoxin inhibit theShaker channel, they must interact differently. The F425GShaker mutation increases charybdotoxin affinity by 3 orders of magnitude but abolishes κ-Pviiasensitivity. The precursor sequence of κ-Pviia was deduced from a cDNA clone, revealing a prepropeptide comprising 72 amino acids. The N-terminal region of the κ-Pviia prepropeptide exhibits striking homology to the ω-, μO-, and δ-conotoxins. Thus, at least four pharmacologically distinct superfamilies ofConus peptides belong to the same “O” superfamily, with the ω- and κ-conotoxins forming one branch, and the δ- and μO-conotoxins forming a second major branch.
Impairment of gaze-directed spatial coding in recent-onset schizophrenia

Patients with schizophrenia show deficits in core cognitive functions as well as in social cognition. The aim of the present study was to test whether deficits in social cognition influence nonsocial, “cold”, cognition. Thirty-five patients with recent-onset schizophrenia (SC) and 30 healthy controls (HC) performed a Simon task with social and simple geometric stimuli. We investigated whether the Simon effect, the slowing of reaction times produced by stimulus incongruities in the task-irrelevant spatial domain, differs between patients and healthy participants as a function of the social nature of the cues. The Simon effect was generated by a schematic drawing of human eyes (social cues) or rectangles (nonsocial cues). Overall, patients had longer reaction times than HC. In the eye-like condition, the Simon effect was significantly stronger for HC than for SC. In HC the Simon effect was significantly stronger in the eye-like than in the rectangle condition. In patients, the Simon effect did not differ significantly between both conditions. Thus, the influence of social cues was greatly reduced in the patient group. Current psychopathology or antipsychotic treatment did not influence results. The present study supports earlier findings of altered processing of schematic social cues in patients with schizophrenia, especially when gaze is task-irrelevant.
Diffuse cystic lung diseases: correlation between radiologic and functional status.

BACKGROUND High-resolution CT (HRCT) scanning plays an important role in the diagnosis of diffuse cystic lung diseases (DCLDs). However, its role in the clinical evaluation of patients affected by DCLD has not yet been well-clarified. At present, pulmonary function tests are the only methods available for the evaluation of lung impairment due to these diseases, but their sensitivity and reliability are still limited. PURPOSE The aim of this study was to correlate the quantitative score of cystic-aerial lesions obtained by a HRCT density mask (DM) software with pulmonary function data in DCLDs. METHODS Spirometry, lung volumes, diffusion capacity, arterial blood gas (ABG) analysis, 6-min walking test (6-MWT), and HRCT with DM quantitative evaluation were performed in a cohort of 25 patients (lymphangioleiomyomatosis [LAM], 13 patients; Langerhans cells histiocytosis [LCH], 12 patients). Linear regression was used for the statistical analysis. The sum and mean of the air-trapping percentages at three different levels of DM study (ie, aortic arch, left lower lobe bronchus origin, and 2 cm from the diaphragmatic muscle), and various functional parameters and exercise performance values were matched for the analysis. RESULTS An obstructive pattern was present in 13 patients (52%; LCH group, 8 patients; LAM group, 5 patients). A predominant restrictive pattern was detected only in three patients (12%; LCH group, two patients; LAM group, one patient). Nine patients (36%) walked < 350 m, and 14 of 23 patients (61%) had a significant decrease in arterial oxygen saturation during exercise (> 4 U). The results of DM quantitative study (sum and mean) significantly correlated with FVC (r = - 0.56; p < 0.001), FEV(1)/vital capacity (r = - 0.94; p < 0.002), midexpiratory phase of forced expiratory flow (r = - 0.84; p < 0.05), FEV(1) (r = - 0.82; p < 0.05), and diffusing capacity of the lung for carbon monoxide (r = - 0.82; p < 0.05), bronchial airway resistance (r = 0.79; p < 0.05), and distance walked on the 6-MWT (r = - 0.53; p < 0.05). No significant correlation was found with the results of ABG analysis. CONCLUSIONS In DCLDs, HRCT scans with quantitative assessment performed by a DM software showed a very good correlation with functional parameters. Therefore, DM could be considered, in combination with a complete functional assessment, in the initial evaluation of patients affected by DCLDs. However, further studies are needed to assess its usefulness in the follow-up of these patients.
A Rapid Antimicrobial Susceptibility Test for Bacillus anthracis

ABSTRACT An effective public health response to a deliberate release of Bacillus anthracis will require a rapid distribution of antimicrobial agents for postexposure prophylaxis and treatment. However, conventional antimicrobial susceptibility testing for B. anthracis requires a 16- to 20-h incubation period. To reduce this time, we have combined a modified broth microdilution (BMD) susceptibility testing method with real-time quantitative PCR (qPCR). The growth or inhibition of growth of B. anthracis cells incubated in 2-fold dilutions of ciprofloxacin (CIP) (0.015 to 16 μg/ml) or doxycycline (DOX) (0.06 to 64 μg/ml) was determined by comparing the fluorescence threshold cycle (CT) generated by target amplification from cells incubated with each drug concentration with the CT of the no-drug (positive growth) control. This ΔCT readily differentiated susceptible and nonsusceptible strains. Among susceptible strains, the median ΔCT values were ≥7.51 cycles for CIP and ≥7.08 cycles for DOX when drug concentrations were at or above the CLSI breakpoint for susceptibility. For CIP- and DOX-nonsusceptible strains, the ΔCT was <1.0 cycle at the breakpoint for susceptibility. When evaluated with 14 genetically and geographically diverse strains of B. anthracis, the rapid method provided the same susceptibility results as conventional methods but required less than 6 h, significantly decreasing the time required for the selection and distribution of appropriate medical countermeasures.
A PBPK Model for Evaluating the Impact of Aldehyde Dehydrogenase Polymorphisms on Comparative Rat and Human Nasal Tissue Acetaldehyde Dosimetry

Inhalation Toxicology International Forum for Respiratory Research Publication details, including instructions for authors and subscription information: http://www.informaworld. com/smpp/title~content=t713657711 A PBPK Model for Evaluating the Impact of Aldehyde Dehydrogenase Polymorphisms on Comparative Rat and Human Nasal Tissue Acetaldehyde Dosimetry Justin G. Teeguarden a; Matthew S. Bogdanffy b; Tammie R. Covington c; Cecilia Tan d; Annie M. Jarabek e a Biological Monitoring and Modeling, Pacific Northwest National Laboratory, Richland, Washington, USA b Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, USA c Human Effectiveness Directorate, Air Force Research Laboratory, Wright Patterson AFB, Dayton, Ohio, USA d The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA e U.S. EPA, Office of Research and Development, National Health Effects Research Laboratory, Experimental Toxicology Division, Pharmacokinetics Branch, Research Triangle Park, North Carolina, USA
Simulation Study of the Layout Technique for P-hit Single-Event Transient Mitigation via the Source Isolation

In this paper, a layout technique for P-hit single-event transient (SET) mitigation via source isolation is studied by way of technology-computer-aided-design numerical simulations. The source-isolation layout design methodology is thoroughly discussed for the combinational standard cell. Based on a 90-nm twin-well CMOS technology, the simulation results indicate that the proposed “radiation hardened by design” (RHBD) technique can significantly reduce SET pulsewidth. The effects of the ion strike angles and strike locations on this hardened technique are also studied, and the area penalty is also discussed. When we combine the layout technique that utilizes the quenching effect with the proposed source-isolation layout technique, the RHBD standard-cell library can be further exploited for additional P-hit SET mitigation in the spaceborne integrated-circuit design.
Role of TCR specificity in CD4+CD25+ regulatory T‐cell selection

Summary: CD4+CD25+ regulatory T cells play a crucial role in preventing autoimmune disease and can also modulate immune responses in settings such as transplantation and infection. We have developed a transgenic mouse system in which the role that T‐cell receptor (TCR) specificity for self‐peptides plays in the formation of CD4+CD25+ regulatory T cells can be examined. We have shown that interactions with a single self‐peptide can induce thymocytes bearing an autoreactive TCR to undergo selection to become CD4+CD25+ regulatory T cells and that thymocytes bearing TCRs with low affinity for the selecting peptide do not appear to undergo selection into this pathway. In addition, thymocytes with identical specificity for the selecting self‐peptide can undergo overt deletion versus abundant selection to become CD4+CD25+ regulatory T cells in response to variations in expression of the selecting peptide in different lineages of transgenic mice. Finally, we have shown that CD4+CD25+ T cells proliferate in response to their selecting self‐peptide in the periphery, but these cells do not proliferate in response to lymphopenia in the absence of the selecting self‐peptide. These studies are determining how the specificity of the TCR for self‐peptides directs the thymic selection and peripheral expansion of CD4+CD25+ regulatory T cells.
Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP‐1

Natural killer (NK) cells are a powerful weapon against viral infections and tumor growth. Although the actin–myosin (actomyosin) cytoskeleton is crucial for a variety of cellular processes, the role of mechanotransduction, the conversion of actomyosin mechanical forces into signaling cascades, was never explored in NK cells. Here, we demonstrate that actomyosin retrograde flow (ARF) controls the immune response of primary human NK cells through a novel interaction between β‐actin and the SH2‐domain‐containing protein tyrosine phosphatase‐1 (SHP‐1), converting its conformation state, and thereby regulating NK cell cytotoxicity. Our results identify ARF as a master regulator of the NK cell immune response. Since actin dynamics occur in multiple cellular processes, this mechanism might also regulate the activity of SHP‐1 in additional cellular systems.
Arteriovenous Fistulas Constructed Using Side-to-Side Anastomosis with Ligation and Division of Distal Venous Arm; A Tertiary Care Hospital Experience

Background and Objective The rising prevalence of end-stage renal disease has added to the demands of renal replacement therapy in the form of hemodialysis (Hd) in lieu of unmitigated needs of renal transplants. The best available angioaccess for HD is the autogenous arteriovenous fistula. Many techniques for arteriovenous anastomosis have been reported, but there is dearth of data which study the side-to-side arteriovenous anastomosis with concomitant ligation and division of the distal venous arm. This study aimed to describe the clinical outcome of the fistulae constructed with this particular technique. Methods It is a descriptive and retrospective review in which all patients who underwent the operation with this particular technique in a certain time period were included. The data entry and analysis was done using SPSS 15. Only descriptive statistics are used. Demographic details, primary patency, end point patency and fistula survival were calculated. Results There were 77 patients, 61 males and 16 females. Radiocephalic arteriovenous anastomosis was constructed in 65 patients, brachiocephalic in 11 patients and brachiobasilic in one patient. Primary patency was 96.1% and end point patency was 90.9% with a median survival of 44 weeks at the end point. Conclusion This particular technique of fistula construction has excellent patency rates, fistula survival and lesser complications when compared to what has been reported for other methods. It is therefore recommended that the technique of angioaccess reported in this study may be considered as a first option.
Autonomy and Interdependence: Beliefs of Brazilian Mothers from State Capitals and Small Towns

This study aimed to investigate characteristics of Brazilian mothers' beliefs system, in the dimensions of autonomy and interdependence. A group of 600 women, half from state capitals and half from small towns, participated in the study. They were individually interviewed with Scales of Allocentrism, Beliefs about Parental Practices and Socialization Goals. Paired and Independent samples t tests and Multivariate GLM were performed. The results indicate that although mothers from both contexts value autonomy, mothers inhabiting small towns considered the relational dimension as the most important; whereas mothers inhabiting capitals valued equally both dimensions, either in their beliefs about practices or in the socialization goals for their children. Mothers from small towns have a higher mean score for allocentrism than mothers living in capitals. Thus, place of residence proved to be a relevant variable in the modulation of maternal beliefs. Educational level was not a significant factor in the variables considered and with this group of mothers. The study results are discussed in terms of their contribution to the understanding of the complex relationship between dimensions of autonomy and interdependence in mothers' beliefs system. El propósito de esta investigación fue investigar las características del sistema de creencias de las madres brasileñas en las dimensiones de autonomía e interdependencia. Participaron en el estudio un grupo de 600 mujeres, la mitad proveniente de la capital y la otra mitad de pequeñas ciudades. Las mujeres fueron individualmente evaluadas en una Escala de Alocentrismo, creencias acerca de prácticas parentales y metas de socialización. Los datos se analizaron en función de pruebas t emparejadas e independientes, y análisis multivariado MLG. Los resultados mostraron que aunque las madres de ambos contextos valoraban la autonomía, las madres de ciudades más pequeñas consideraron más importante la dimensión relacional; mientras que las madres provenientes de capitales valoraban por igual las dimensiones relativas a su sistema de creencias parentales y las metas de socialización. Por otra parte, las madres de ciudades más pequeñas obtuvieron mayores puntuaciones en alocentrismo que las madres de las capitales. Asimismo, el lugar de residencia se consideró como un factor relevante en la modulación del sistema de creencias maternas. El nivel educativo no fue un factor significativo en las variables evaluadas ni con la muestra utilizada. En general, los resultados del estudio se discuten en términos de su contribución para la compresión de las complejas relaciones entre las dimensiones de autonomía e interdependencia en el sistema de creencias de las madres.
INTRAOCULAR PRESSURE CHANGES DURING VITRECTOMY USING CONSTELLATION VISION SYSTEM'S INTRAOCULAR PRESSURE CONTROL FEATURE

Purpose: To evaluate intraocular pressure (IOP) changes during experimental vitrectomy and the efficacy of Constellation Vision System's IOP control (IOPc) feature in reestablishing baseline pressure. Methods: Using a pressure transducer in freshly enucleated porcine eyes, a broad range of parameters (baseline pressures, aspiration levels, and cut rates) were tested with 23- and 25-gauge probes and IOPc turned ON versus OFF. Results: IOPc turned ON was significantly more effective than IOPc turned OFF in controlling IOP drop and stabilizing pressure during vitrectomy using a wide range of baseline pressures (20–70 mmHg). The 23-gauge system consistently presented a reduced drop from baseline compared with the 25-gauge system. The overall average drop for the 23- and 25-gauge systems was 12.79 mmHg and 21.17 mmHg, respectively. Both gauge sizes reestablished baseline pressure approximately 1.6 seconds after the initial pressure drop generated at the beginning of aspiration. A peak of IOP (overshooting) was observed when the pressure was returning to baseline using both 23- and 25-gauge systems. Conclusion: Using IOPc feature turned ON, 23- and 25-gauge probes were effective in reestablishing and sustaining baseline infusion pressures, although 23-gauge probes showed less IOP fluctuation than did 25-gauge probes.
Glucose Toxicity

Glucose toxicity is a well-established entity that has been shown in animal models of diabetes to contribute to development of insulin resistance and impaired insulin secretion. In type II (non-insulin-dependent) diabetes in humans, a considerable body of evidence has accumulated indicating that a chronic physiological increment in the plasma glucose concentration leads to progressive impairment in insulin secretion and may contribute to insulin resistance as well. The precise biochemical mechanism(s) responsible for the hyperglycemia-induced defect in insulin secretion remains to be defined but may be related to a defect in phosphoinositide metabolism. In animal models of diabetes, development of insulin resistance is related to downregulation of the glucose-transport system, and a similar phenomenon is also likely to occur in humans. In addition, hyperglycemia in humans may lead to a defect in glycogen synthesis. In this respect, humans may be different from rats. In type I (insulin-dependent) diabetic patients who are poorly controlled, insulin resistance is a characteristic feature and can be ameliorated by tight glycemic control, suggesting that hyperglycemia is responsible for the insulin resistance. Evidence also has accumulated to implicate glucose toxicity in the functional impairment in insulin secretion that occurs during the initial presentation of patients with type I diabetes, and this may explain the honeymoon period so commonly observed after the institution of insulin therapy.