Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasticity of vagal brainstem circuits in the control of gastric function

Background Sensory information from the viscera, including the gastrointestinal (GI) tract, is transmitted through the afferent vagus via a glutamatergic synapse to neurons of the nucleus tractus solitarius (NTS), which integrate this sensory information to regulate autonomic functions and homeostasis. The integrated response is conveyed to, amongst other nuclei, the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV) using mainly GABA, glutamate and catecholamines as neurotransmitters. Despite being modulated by almost all the neurotransmitters tested so far, the glutamatergic synapse between NTS and DMV does not appear to be tonically active in the control of gastric motility and tone. Conversely, tonic inhibitory GABAergic neurotransmission from the NTS to the DMV appears critical in setting gastric tone and motility, yet, under basal conditions, this synapse appears resistant to modulation.
Do Symptoms of ADHD at Ages 7 and 10 Predict Academic Outcome at Age 16 in the General Population?

Objective: To examine the value of the Conners 10-item scale to predict academic outcomes at age 16 years in schoolchildren aged 7 and 10 years. Method: A cohort study of N = 544 children in a municipality of Stockholm County was conducted. Using the parent and teacher version of the Conners 10-item scale, 7- and 10-year-olds were screened for ADHD symptoms and followed-up for school outcome at age 16 years. Results: The best predictors for school outcome at age 16 years were the Conners items, “child failing to finish tasks” and “being inattentive, easily distracted,” with a high specificity (90%-97%) but low sensitivity (18%-39%). Conclusion: This study indicates a considerable association between certain symptoms of inattentiveness in young schoolchildren and academic underachievement at age 16 years. Screening for one to two symptoms of inattention in schoolchildren identifies 30% to 40% of participants at risk for later poor school attainment.
Thermogenic and corticosterone responses to intravenous cytokines (IL-1beta and TNF-alpha) are attenuated by subdiaphragmatic vagotomy.

The brain orchestrates changes in behavior and physiology as a consequence of peripheral immune activation and infection. These changes require that the brain receives signals from the periphery that an immunological challenge has occurred. Previous research has established that cytokines play a role in signalling the brain. What remains unclear, however, is how peripheral cytokines signal the central nervous system. A recent proposal is that cytokines signal the brain by stimulating peripheral nerves. The hypothesis states that following infection and the release of cytokines such as IL-1beta into local tissue or microvasculature, IL-1beta stimulates IL-1 receptors on vagal afferent terminals, or more likely on cells of vagal paraganglia. Vagal afferents, in turn, signal the brain. Previous work has demonstrated that transection of the vagus below the level of the diaphragm blocks or attenuates many illness consequences of intraperitoneally (i.p.) administered lipopolysaccharide (LPS) or IL-1beta. The present studies extend these findings by examining the effect of subdiaphragmatic vagotomy on illness consequences following intravenously (i.v.) administered IL-1beta and TNF-alpha. Subdiaphragmatic vagotomy attenuated both the fever response and corticosterone response produced by i.v. administered cytokines. This effect was dose dependent. The results add support to the hypothesis that vagal afferents are involved in peripheral cytokine-to-brain communication.
Copper and Iron Are the Limiting Factors for Growth of the Yeast Saccharomyces cerevisiae in an Alkaline Environment*

Exposure of the yeast Saccharomyces cerevisiae to an alkaline environment represents a stress situation that negatively affects growth and results in an adaptive transcriptional response. We screened a collection of 4825 haploid deletion mutants for their ability to grow at mild alkaline pH, and we identified 118 genes, involved in numerous cellular functions, whose absence results in reduced growth. The list includes several key genes in copper and iron homeostasis, such as CCC2, RCS1, FET3, LYS7, and CTR1. In contrast, a screen of high-copy number plasmid libraries for clones able to increase tolerance to alkaline pH revealed only two genes: FET4 (encoding a low affinity transporter for copper, iron, and zinc) and CTR1 (encoding a high affinity copper transporter). The beneficial effect of overexpression of CTR1 requires a functional high affinity iron transport system, as it was abolished by deletion of FET3, a component of the high affinity transport system, or CCC2, which is required for assembly of the transport system. The growth-promoting effect of FET4 was not modified in these mutants. These results suggest that the observed tolerance to alkaline pH is because of improved iron uptake and indicate that both iron and copper are limiting factors for growth under alkaline pH conditions. Addition to the medium of micromolar concentrations of copper or iron ions drastically improved growth at high pH. Supplementation with iron improved somewhat the tolerance of a fet3 strain but was ineffective in a ctr1 mutant, suggesting the existence of additional copper-requiring functions important for tolerance to an alkaline environment.
Epidermal growth factor receptor juxtamembrane region regulates allosteric tyrosine kinase activation

Structural studies of the extracellular and tyrosine kinase domains of the epidermal growth factor receptor (ErbB-1) provide considerable insight into facets of the receptor activation mechanism, but the contributions of other regions of ErbB-1 have not been ascertained. This study demonstrates that the intracellular juxtamembrane (JM) region plays a vital role in the kinase activation mechanism. In the experiments described herein, the entire ErbB-1 intracellular domain (ICD) has been expressed in mammalian cells to explore the significance of the JM region in kinase activity. Deletion of the JM region (ΔJM) results in a severe loss of ICD tyrosine phosphorylation, indicating that this region is required for maximal activity of the tyrosine kinase domain. Coexpression of ΔJM and dimerization-deficient kinase domain ICD mutants revealed that the JM region is indispensable for allosteric kinase activation and productive monomer interactions within a dimer. Studies with the intact receptor confirmed the role of the JM region in kinase activation. Within the JM region, Thr-654 is a known protein kinase C (PKC) phosphorylation site that modulates kinase activity in the context of the intact ErbB-1 receptor; yet, the mechanism is not known. Whereas a T654A mutation promotes increased ICD tyrosine phosphorylation, the phosphomimetic T654D mutant generates a 50% reduction in ICD tyrosine phosphorylation. Similar to the ΔJM mutants, the T654D mutant ICD failed to interact with a wild-type monomer. This study reveals an integral role for the intracellular JM region of ErbB-1 in allosteric kinase activation.
An Efficient High-Power Fundamental Oscillator Above $f_{\max }/2$ : A Systematic Design

A novel approach to design efficient high-output-power fundamental oscillators beyond <inline-formula> <tex-math notation="LaTeX">$f_{\max }/2$ </tex-math></inline-formula> of the employed process is presented. The idea is to shape and maximize the unilateral power gain (<inline-formula> <tex-math notation="LaTeX">$U$ </tex-math></inline-formula>) of the network at the desired frequency using optimum passive internal and external feedback networks. The proposed technique significantly improves the output power and dc-to-RF efficiency of the oscillator. To show the feasibility of this novel approach, a 175 GHz fundamental oscillator is designed in a 130 nm SiGe BiCMOS process (<inline-formula> <tex-math notation="LaTeX">$f_{\max }\simeq ~280$ </tex-math></inline-formula> GHz), which achieves a measured dc-to-RF efficiency of 11.7% that is markedly higher than all reported oscillators above <inline-formula> <tex-math notation="LaTeX">$f_{\max }/3$ </tex-math></inline-formula> of their active device. Measurements show that the designed oscillator generates a peak power of 3 mW (4.8 dBm) with a phase noise figure of merit (FoM) of −195.4 dBc/Hz at 1 MHz offset frequency, which is the highest phase noise FoM among all reported CMOS/BiCMOS millimeter-wave and terahertz oscillators. The proposed method considers the possible process, voltage, temperature variations as well as modeling errors of the passive components in the design stage.
Prebending the estrogen response element destabilizes binding of the estrogen receptor DNA binding domain

Binding of many eukaryotic transcription regulatory proteins to their DNA recognition sequences results in conformational changes in DNA. To test the effect of altering DNA topology by prebending a transcription factor binding site, we examined the interaction of the estrogen receptor (ER) DNA binding domain (DBD) with prebent estrogen response elements (EREs). When the ERE in minicircle DNA was prebent toward the major groove, which is in the same direction as the ER-induced DNA bend, there was no significant effect on ER DBD binding relative to the linear counterparts. However, when the ERE was bent toward the minor groove, in a direction that opposes the ER-induced DNA bend, there was a four- to eightfold reduction in ER DBD binding. Since reduced binding was also observed with the ERE in nicked circles, the reduction in binding was not due to torsional force induced by binding of ER DBD to the prebent ERE in covalently closed minicircles. To determine the mechanism responsible for reduced binding to the prebent ERE, we examined the effect of prebending the ERE on the association and dissociation of the ER DBD. Binding of the ER DBD to ERE-containing minicircles was rapid when the EREs were prebent toward either the major or minor groove of the DNA (k(on) of 9.9 x 10(6) to 1.7 x 10(7) M(-1) s(-1)). Prebending the ERE toward the minor groove resulted in an increase in k(off) of four- to fivefold. Increased dissociation of the ER DBD from the ERE is, therefore, the major factor responsible for reduced binding of the ER DBD to an ERE prebent toward the minor groove. These data provide the first direct demonstration that the interaction of a eukaryotic transcription factor with its recognition sequence can be strongly influenced by altering DNA topology through prebending the DNA.
Fluorine-18-fluoromisonidazole radiation dosimetry in imaging studies.

UNLABELLED Fluoromisonidazole (FMISO), labeled with the positron emitter 18F, is a useful hypoxia imaging agent for PET studies, with potential applications in patients with tumors, cardiovascular disease and stroke. METHODS Radiation doses were calculated in patients undergoing imaging studies to help define the radiation risk of FMISO-PET imaging. Time-dependent concentrations of radioactivity were determined in blood samples and PET images of patients following intravenous injection of [18F]FMISO. Radiation absorbed doses were calculated using the procedures of the Medical Internal Radiation Dose (MIRD) committee, taking into account the variation in dose based on the distribution of activities observed in the individual patients. As part of this study we also calculated an S value for brain to eye. Effective dose equivalent was calculated using ICRP 60 weights. RESULTS Effective dose equivalent was 0.013 mSv/MBq in men and 0.014 mSv/MBq in women. Individual organ doses for women were not different from men. Assuming bladder voiding at 2- or 4-hr intervals, the critical organ that received the highest dose was the urinary bladder wall (0.021 mGy/MBq with 2-hr voiding intervals or 0.029 mGy/MBq with 4-hr voiding intervals). CONCLUSION The organ doses for [18F]FMISO are comparable to those associated with other commonly performed nuclear medicine tests and indicate that potential radiation risks associated with this study are within generally accepted limits.
Identification of the cellular mechanisms responsible for platelet‐derived growth factor induced alterations in cytoplasmic vinculin distribution

Exposure of quiescent density arrested BALB/c‐3T3 cells (clone A31) to platelet‐derived growth factor (PDGF;6–12 ng/ml) results in a rapid, reversible, time‐and dose‐dependent removal of vinculin from adhesion plaques (Herman and Pledger, 1985). Potential cellular mechanisms involved in PDGF‐induced removal of vinculin from adhesion plaques were examined. Removal of vinculin from adhesion plaques following exposure of cells to PDGF was temperature dependent, occurred in many fibroblast cell lines, and could be mimicked by 12‐tetradecanoyl phorbol‐13‐acetate (TPA; 5‐125 nM) or melittin (0.35 μM). Unlike the effect of PDGF, TPA‐or melittin‐induced vinculin disruption was not reversible. The removal of vinculin from adhesion plaques was inhibited by trifluoroperazine (TFP; 2.5 μM). 8‐(N,N‐diethylamino) octyl‐3,4,5‐trimethoxy benzoate (TMB‐8; 1.0 μM), mepacrine (220 μM), n‐α‐p‐tosyl‐L‐lysine chloromethylketone (TLCK; 100 μM), phenylmethoxysulphonylfluoride (PMSF; 500 μM), and e‐aminocaproic acid (e‐ACA; 100 μM); however, amiloride (100 μM), A23187 (20 μM), and chloroquine (1 mM) were unable to inhibit this effect. Melittin disruption of vinculin was inhibited by (in order of decreasing effectiveness) mepacrine > TMB‐8 > TFP > leupeptin > PMSF, whereas A23187 and amiloride had no effect. The return of vinculin to adhesion plaques following PDGF treatment required de novo mRNA transcription and protein synthesis and was associated with PDGF‐stimulated synthesis of vinculin.
Correlates of verbal learning and memory after pediatric traumatic brain injury

ABSTRACT This study examined the role of injury-related variables, socioeconomic disadvantage, and preexisting conditions on verbal learning and memory in a sample of children with traumatic brain injury (TBI). We also explored the mediating effect of processing speed and working memory. One hundred children aged 7–16 years (M = 13.46, SD = 2.78) completed a neuropsychological assessment between 1–12 months post injury. Hierarchical multiple regression analyses were conducted on domains comprising the four-factor model of the California Verbal Learning Test–Children’s Version (CVLT–C). Results revealed independent associations between injury severity as well as parental education on learning efficiency and delayed recall, while injury severity alone accounted for inaccurate recall. Working memory and prior special education placement were predictive of the attention factor of the CVLT–C. Additionally, Sobel tests showed that working memory mediated the effect of prior special education on learning efficiency (Z = 2.90, p < 0.01) and delayed recall (Z = 2.82, p < 0.01). Working memory was unrelated to injury severity. No evidence for a mediating effect of processing speed was found. The findings emphasize the importance of considering the impact of socioeconomic disadvantage and pre-injury conditions in addition to injury-related factors on outcomes of TBI.
Well-being and Anticipation for Future Positive Events: Evidences from an fMRI Study

Anticipation for future confers great benefits to human well-being and mental health. However, previous work focus on how people’s well-being correlate with brain activities during perception of emotional stimuli, rather than anticipation for the future events. Here, the current study investigated how well-being relates to neural circuitry underlying the anticipating process of future desired events. Using event-related functional magnetic resonance imaging, 40 participants were scanned while they were performing an emotion anticipation task, in which they were instructed to anticipate the positive or neutral events. The results showed that bilateral medial prefrontal cortex (MPFC) were activated during anticipation for positive events relative to neutral events, and the enhanced brain activation in MPFC was associated with higher level of well-being. The findings suggest a neural mechanism by which the anticipation process to future desired events correlates to human well-being, which provide a future-oriented view on the neural sources of well-being.
Catheter Salvage After Catheter-Related Bloodstream Infection During Home Parenteral Nutrition

Background: Catheter-related bloodstream infection (CRBSI) is a common complication in patients receiving home parenteral nutrition (HPN). Data regarding catheter salvage after a CRBSI episode are limited. We aimed to determine the incidence of CRBSI and rates of catheter salvage in adult patients receiving HPN. Materials and Methods: We retrospectively searched our prospectively maintained HPN database for the records of all adult patients receiving HPN from January 1, 1990, to December 31, 2013, at our tertiary referral center. Data abstracted from the medical records included demographics, diseases, treatments, and outcomes. The incidence of CRBSI and rates of catheter salvage were determined. Results: Of 1040 patients identified, 620 (59.6%) were men. The median total duration on HPN was 124.5 days (interquartile range, 49.0–345.5 days). Mean (SD) age at HPN initiation was 53.3 (15.3) years. During the study period, 465 CRBSIs developed in 187 patients (18%). The rate of CRBSI was 0.64/1000 catheter days. Overall, 70% of catheters were salvaged (retained despite CRBSI) during the study period: 78% of infections with coagulase-negative staphylococci, 87% with methicillin-sensitive Staphylococcus aureus, and 27% with methicillin-resistant S aureus. The percentage of catheters salvaged was 63% from 1990 to 1994, 63% from 1995 to 1999, 61% from 2000 to 2004, 72% from 2005 to 2009, and 76% from 2010 to 2013. Conclusion: Catheter salvage is possible after a CRBSI episode. Since most episodes of CRBSI are caused by skin commensals, effective treatment without removal of the central venous catheter is possible in most cases.
Unraveling Single-Particle Trajectories Confined in Tubular Networks

The analysis of single particle trajectories plays an important role in elucidating dynamics within complex environments such as those found in living cells. However, the characterization of intracellular particle motion is often confounded by confinement of the particles within non-trivial subcellular geometries. Here, we focus specifically on the case of particles undergoing Brownian motion within a tubular network, as found in some cellular organelles. An unraveling algorithm is developed to uncouple particle motion from the confining network structure, allowing for an accurate extraction of the diffusion coefficient, as well as differentiating between Brownian and fractional Brownian dynamics. We validate the algorithm with simulated trajectories and then highlight its application to an example system: analyzing the motion of membrane proteins confined in the tubules of the peripheral endoplasmic reticulum in mammalian cells. We show that these proteins undergo diffusive motion with a well-characterized diffusivity. Our algorithm provides a generally applicable approach for disentangling geometric morphology and particle dynamics in networked architectures.
GENETICS OF MIMICRY IN THE TIGER SWALLOWTAIL BUTTERFLIES, PAPILIO GLAUCUS AND P. CANADENSIS (LEPIDOPTERA: PAPILIONIDAE)

The tiger swallowtail butterfly, Papilio glaucus, exhibits a female‐limited polymorphism for Batesian mimicry; the Canadian tiger swallowtail, Papilio canadensis, lacks the mimetic (dark) form entirely. The species hybridize to a limited extent where their ranges overlap. Field collections and censuses indicate that mimetic females occur throughout the range of P. glaucus but at lowest frequencies in populations at the latitudinal edges of its geographic range such as the southernmost part of Florida and along the entire northern edge of its distribution from Massachusetts to Minnesota. Frequencies of mimetic females have remained relatively stable over time. Inheritance of the mimetic form is controlled primarily by two interacting sex‐linked loci. The typical matrilineal pattern of inheritance in P. glaucus can be explained by polymorphism at a Y‐linked locus, b. Analysis of P. glaucus × P. canadensis crosses has also revealed an X‐linked locus, s, which controls the expression of the mimetic phenotype. The P. canadensis allele, scan, suppresses the mimetic phenotype in hybrid and backcross females. Results from more than 12 yr of rearing tiger swallowtails, including interspecies hybrids, indicate that the absence of mimetic P. canadensis females is due to both a high frequency of the “suppressing” allele scan and low frequency of the black‐pigment‐determining b + allele. The frequency of scan (or other suppressing alleles of s) in P. glaucus populations outside the hybrid zone is low. Some males heterozygous at the s locus and some suppressed mimetic females occur within the hybrid zone. A simple genetic model predicts the frequency of daughters that differ in phenotype from their mothers.
Demographics and outcome of elective cerclage in a multi-ethnic London district general hospital

Summary Elective cerclage is a rare procedure, but is reported to be relatively more common in developing countries. This variation in rate may be reflected in a multi-ethnic population as seen in London. Our study analysed the epidemiology and rate of elective cerclage performed in a London district general hospital. Factors contributing to the outcome of the procedures were also reviewed. A total of 41 elective cerclages were performed in the hospital between 2000 and 2007. Data from these were collected retrospectively, including maternal history, operative details, and gestational age at delivery. Fisher's exact test was used for statistical analysis. Of the 41 cases, 19 pregnancies were carried to term (≥37 weeks' gestation), nine were pre-term (24–36 weeks' gestation) and seven miscarried (<24 weeks' gestation); six cases had not yet delivered. All of the patients were immigrants from developing countries but ethnicity did not affect the operative outcome (p = 0.89, Fisher's exact). The other factors studied were also noted to have no significant impact on success. These included cervical length at insertion (p = 1.00, Fisher's exact), type of suture (p = 0.90, Fisher's exact) and average gestation at insertion (p = 0.20, Fisher's exact). In conclusion, all patients requiring intervention in this study originated from developing countries. This is a disproportionately high figure relative to the demographic breakdown of the study population. Such a finding may be due to geographical variation of risk factors for cervical incompetence but may also be influenced by observer bias. Additional studies are needed to further investigate the influence of ethnicity on the rate of elective cerclage. None of the variables analysed in this study significantly affected the outcome of the procedure.