Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteomic Identification of Novel Substrates of a Protein Isoaspartyl Methyltransferase Repair Enzyme*

We report the use of a proteomic strategy to identify hitherto unknown substrates for mammalian protein l-isoaspartate O-methyltransferase. This methyltransferase initiates the repair of isoaspartyl residues in aged or stress-damaged proteins in vivo. Tissues from mice lacking the methyltransferase (Pcmt1-/-) accumulate more isoaspartyl residues than their wild-type littermates, with the most “damaged” residues arising in the brain. To identify the proteins containing these residues, brain homogenates from Pcmt1-/- mice were methylated by exogenous repair enzyme and the radiolabeled methyl donor S-adenosyl-[methyl-3H]methionine. Methylated proteins in the homogenates were resolved by both one-dimensional and two-dimensional electrophoresis, and methyltransferase substrates were identified by their increased radiolabeling when isolated from Pcmt1-/- animals compared with Pcmt1+/+ littermates. Mass spectrometric analyses of these isolated brain proteins reveal for the first time that microtubule-associated protein-2, calreticulin, clathrin light chains a and b, ubiquitin carboxyl-terminal hydrolase L1, phosphatidylethanolamine-binding protein, stathmin, β-synuclein, and α-synuclein, are all substrates for the l-isoaspartate methyltransferase in vivo. Our methodology for methyltransferase substrate identification was further supplemented by demonstrating that one of these methyltransferase targets, microtubule-associated protein-2, could be radiolabeled within Pcmt1-/- brain extracts using radioactive methyl donor and exogenous methyltransferase enzyme and then specifically immunoprecipitated with microtubule-associated protein-2 antibodies to recover co-localized protein with radioactivity. We comment on the functional significance of accumulation of relatively high levels of isoaspartate within these methyltransferase targets in the context of the histological and phenotypical changes associated with the methyltransferase knock-out mice.
Cell cycle control of PDGF‐induced Ca2+ signaling through modulation of sphingolipid metabolism

The effects of growth factors have been shown to depend on the position of a cell in the cell cycle. However, the physiological basis for this phenomenon remains unclear. Here we show that the majority of both CEINGE clone3 (cl3) and human embryonic kidney 293 cells, when arrested in a quiescent phase (G0), responded to platelet‐derived growth factor BB (PDGF‐BB) with non‐oscillatory Ca2+ signals. Furthermore, the same type of Ca2+ response was also observed in CEINGE cl3 cells (and to a lesser extent in HEK 293 cells) blocked at the G1/S boundary. In contrast, CEINGE cl3 cells synchronized in early G1 or released from G1/S arrest responded in an oscillatory fashion. This cell cycle‐dependent modulation of Ca2+ signaling was not observed on epidermal growth factor and G‐protein‐coupled receptor stimulation and was not due to differences in the expression of PDGF receptors (PDGFRs) during the cell cycle. We demonstrate that inhibition of sphingosine‐kinase, which converts sphingosine to sphingosine‐1‐phosphate, caused G0 as well as G1/S synchronized cells to restore the oscillatory Ca2+ response to PDGF‐BB. In addition, we show that the synthesis of sphingosine and sphingosine‐1‐phosphate is regulated by the cell cycle and may underlie the differences in Ca2+ signaling after PDGFR stimulation. —Fatatis, A. , Miller, R. J. Cell cycle control of PDGF‐induced Ca2+ signaling through modulation of sphingolipid metabolism. FASEB J. 13, 1291–1301 (1999)
Term newborns who are at risk for sepsis: are lumbar punctures necessary?

OBJECTIVES To determine: (1) whether a lumbar puncture (LP) is indicated in asymptomatic full-term newborns delivered by mothers at risk of intrapartum sepsis; and (2) whether gentamicin improves bacterial coverage for such newborns when used with ampicillin. DESIGN A retrospective chart review from 1987 through 1993 of all newborns with positive blood and/or cerebrospinal fluid cultures in the first 7 days of life. METHODS Pregnant women were screened in the second trimester for group B streptococci and given ampicillin during labor if two or more risk factors were present: group B streptococci colonization, maternal fever or leukocytosis, rupture of membranes at more than 18 hours, foul-smelling amniotic fluid, and fetal tachycardia. After sepsis evaluation (LP, blood culture, white blood cell count, and differential), asymptomatic infants received ampicillin and gentamicin for 48 to 72 hours unless cultures grew pathogens. RESULTS Of approximately 24 452 full-term births in 7 years, 7% (1712) had evaluations for symptoms of sepsis, and 14% (3423) were asymptomatic but had evaluations for maternal risk factors. There were 11 cases of meningitis, all involving symptomatic newborns; 10 of these 11 had positive blood cultures for the same organism. In asymptomatic infants, none of the 3423 had meningitis (95% confidence interval, 0 to 0.0008), although 35 grew contaminants. Of 73 pathogens isolated from blood or cerebrospinal fluid, 7 (9.5%) were resistant to ampicillin. Addition of gentamicin provided coverage for only 2 of these 7 pathogens. Of 5135 infants who received ampicillin and gentamicin, only 2 required gentamicin for improved coverage. CONCLUSIONS (1) LP is unnecessary in asymptomatic full-term newborns. (2) Empiric coverage for asymptomatic newborns with maternal risk factors need not include gentamicin at all hospitals, because it only improved the coverage of ampicillin alone from 90% to 93% of pathogens, but it exposed more than 5000 infants to the side effects of gentamicin. (3) The presence of leukopenia (<5000 white blood cells/mm) is highly predictive of bacteremia.
Fractal Patterns Created by Ulam's Cellular Automaton

Ulam's cellular automaton, a nonlinear two-dimensional cellular automaton, was introduced by Stanislaw Ulam for emulating crystalline growths. In this paper we give two numerical results in which the particular orbit of the automaton has some fractal structures. First result is that the boundaries of the spatio patterns are fractal curves as time approaches infinity. Second, we study the number of cells consisting the spatio patterns for each time step. We show that the dynamics of the number can be represented by Lebesgue's singular function.
Dynamic Restructuring in an Experimental Operating System

A well-structured system can easily be understood and modified. Moreover, it may lend itself even to dynamic modification: under special conditions, the possibility of changing system parts while the system is running can be provided at little additional cost. Our approach to the design of dynamically modifiable systems is based on the principle of data abstraction applied to types and modules. It allows for dynamic replacement or restructuring of a module's implementation if this does not affect its specification (or if it leads to some kdnd of compatible specification). The fundamental principles of such "replugging" are exhibited, and the implementation of a replugging facility for an experimental operating system on a PDP-11/40E is described.
Effect of Characteristics Breeding Site Againts Density of Larva Anopheles in Tegalombo Sub District Pacitan Indonesia

The purpose ofthe studywas to determinethe influence ofbreeding siteon thedensity oflarvalAnophelesbreedinginthe VillageNgreco District ofTegalomboPacitan Indonesia. The study wasobservationalwithcross sectionalapproachconductedinfoursubdistrictHamletVillageNgrecoTegalomboPacitanin May-June 2014. The population and the sample contained 15 breeding sites of Anopheles larvae were found in four hamlets namely Krajan, Gamping, Nglodo, and Jajar in the village Ngreco. Accidentalsamplingis asampling. The analysis used ismultiple linear regressionwithɑ =0. 05. The results of the study of Anopheleslarvae breeding sites found as many as 10 pools, 2 rivers, and 3 paddy. based onmultiple linear regression. The influenceof thedensity ofAnopheleslarvaeistemperature (p =0. 006, p <0. 05), humidity (p =0. 002, p <0. 05), Animalwater (p =0. 000, p <0. 05). Multivariate analysis with multiple linear regression found that temperature, humidity and animal water related to the density of Anopheles larvae. Advice toagenciesandthe publictoalwaysmonitor theplaceas a potentialbreeding ground forAnopheleslarvaeand the eradication ofAnopheleslarvaetothe publicfree ofmalaria.
Physical mapping of 5S and 18S ribosomal DNA in three species of Agave (Asparagales, Asparagaceae)

Abstract Agave Linnaeus, 1753 is endemic of America and is considered one of the most important crops in Mexico due to its key role in the country’s economy. Cytogenetic analysis was carried out in Agave tequilana Weber, 1902 ‘Azul’, Agave cupreata Trelease et Berger, 1915 and Agave angustifolia Haworth, 1812. The analysis showed that in all species the diploid chromosome number was 2n = 60, with bimodal karyotypes composed of five pairs of large chromosomes and 25 pairs of small chromosomes. Furthermore, different karyotypical formulae as well as a secondary constriction in a large chromosome pair were found in all species. Fluorescent in situ hybridization (FISH) was used for physical mapping of 5S and 18S ribosomal DNA (rDNA). All species analyzed showed that 5S rDNA was located in both arms of a small chromosome pair, while 18S rDNA was associated with the secondary constriction of a large chromosome pair. Data of FISH analysis provides new information about the position and number of rDNA loci and helps for detection of hybrids in breeding programs as well as evolutionary studies.
Effects of sensitivity to life stress on uncinate fasciculus segments in early adolescence

Abstract Previous research suggests that exposure to early life stress (ELS) affects the structural integrity of the uncinate fasciculus (UF), a frontolimbic white matter tract that undergoes protracted development throughout adolescence. Adolescence is an important transitional period characterized by the emergence of internalizing psychopathology such as anxiety, particularly in individuals with high levels of stress sensitivity. We examined the relations among sensitivity to ELS, structural integrity of the UF, and anxiety symptoms in 104 early adolescents. We conducted structured interviews to assess exposure to ELS and obtained subjective and objective ratings of stress severity, from which we derived an index of ELS sensitivity. We also acquired diffusion MRI and conducted deterministic tractography to visualize UF trajectories and to compute measures of structural integrity from three distinct segments of the UF: frontal, insular, temporal. We found that higher sensitivity to ELS predicted both reduced fractional anisotropy in right frontal UF and higher levels of anxiety symptoms. These findings suggest that fibers in frontal UF, which are still developing throughout adolescence, are most vulnerable to the effects of heightened sensitivity to ELS, and that reduced structural integrity of frontal UF may underlie the relation between early stress and subsequent internalizing psychopathology.
Connexin 43 controls the multipolar phase of neuronal migration to the cerebral cortex

The prospective pyramidal neurons, migrating from the proliferative ventricular zone to the overlaying cortical plate, assume multipolar morphology while passing through the transient subventricular zone. Here, we show that this morphogenetic transformation, from the bipolar to the mutipolar and then back to bipolar again, is associated with expression of connexin 43 (Cx43) and, that knockdown of Cx43 retards, whereas its overexpression enhances, this morphogenetic process. In addition, we have observed that knockdown of Cx43 reduces expression of p27, whereas overexpression of p27 rescues the effect of Cx43 knockdown in the multipolar neurons. Furthermore, functional gap junction/hemichannel domain, and the C-terminal domain of Cx43, independently enhance the expression of p27 and promote the morphological transformation and migration of the multipolar neurons in the SVZ/IZ. Collectively, these results indicate that Cx43 regulates the passage of migrating neurons through their multipolar stage via p27 signaling and that interference with this process, by either genetic and/or environmental factors, may cause cortical malformations.
A viral CTL escape mutation leading to immunoglobulin-like transcript 4–mediated functional inhibition of myelomonocytic cells

Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversification.
Evaluation of the effectiveness of diagnostic & management decision by teleophthalmology using indigenous equipment in comparison with in-clinic assessment of patients

Background & objectives: There is a concern on the quality and the usefulness of teleophthalmology images, particularly those using indigenous equipment, in making a diagnosis and treatment decisions in ophthalmology. The present study was done to compare the level of agreement and sensitivity and specificity of diagnosis and management decisions of various eye diseases by teleophthalmology using indigenous equipment, compared to the in-clinic assessment. Methods: Patients having different eye diseases were evaluated by two ophthalmologists – one ophthalmologist examined the patient in clinic setting while the other ophthalmologist made the diagnosis and management decision based on images sent by teleophthalmology. The images were taken by the ophthalmic technician using digital imaging system and fundus camera. The clinical findings and management decisions by the two ophthalmologists were masked to each others. Results: In diagnosis of anterior segment eye diseases such as cataract and corneal diseases there was good to very good agreement (kappa values of 0.68 and 0.91 for cataract and corneal diseases respectively) between in-clinic assessment and assessment by teleophthalmology. There was moderate agreement (kappa values of 0.52 and 0.48 for glaucoma and retinal diseases respectively) between in-clinic assessment and assessment by teleophthalmology for the diagnosis of glaucoma and retinal diseases. For the management decisions of patients, there was moderate level of agreement in all groups of eye diseases. Interpretation & conclusions: Teleophthalmology, using indigenous equipment was found to be effective in diagnosis and management decision of anterior segment eye diseases such as cataract and cornea, and with some modification and continuous training to the technicians could become an effective tool for screening and referral of glaucoma and retinal diseases.
Do They Need Goals or Support? A Report from a Goal-Setting Intervention Using Physical Activity Monitors in Youth

The objective of this study was to investigate the association between physical activity (PA) and different goal setting and strategies in youth. The study took into consideration different sources of support as well as gender variations. Classmate and Teacher Support scales were used to evaluate support in physical education (PE) classes, and moderate-to-vigorous physical activity (MVPA) was reported. Garmin Vivofit® activity trackers were used during an 8 week-long intervention to count daily steps. Data was collected from 65 adolescents (mean age 17.2 ± 0.2), 74 young adolescents (mean age 15.3 ± 0.2) and 57 children (mean age 11.5 ± 0.4). An experimental design was employed, with “goal” and “do your best” groups given different step goal strategies. The results show that both groups achieved a comparable number of steps. Two-way ANOVA showed interactional effects between gender and teacher support. There were no such effects for MVPA and number of steps. Although classmate support in PE was reported to be reasonably high, the findings show that it does not play a significant role in increasing MVPA behaviors in youths. However, the problem of significantly lower support given to adolescent girls by PE teachers should be embedded into the teaching context of PE students and counteracted in school setting realities.
Innate Lymphoid Cells Groups 1 and 3 in the Epithelial Compartment of Functional Human Intestinal Allografts

We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103+ cells) principally due to reduced CD3+CD8+ cells, while CD103+CD3– cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3– IELs were significantly higher in patients receiving corticosteroids. Compared with controls, more CD3– IELs of the grafts expressed CD56, NKp44, interleukin (IL)‐23 receptor, retinoid‐related orphan receptor gamma t (RORγt), and CCR6. No difference was observed in granzyme B, and CD3–CD127+ cells were more abundant in native intestines. Ex vivo, and after in vitro activation, CD3– IELs in grafts produced significantly more interferon (IFN)‐γ and IL‐22, and a double IFNγ+IL‐22+ population was observed. Epithelial cell–depleted grafts IELs were cytotoxic, whereas this was not observed in controls. In conclusion, different from native intestines, a CD3– IEL subset predominates in grafts, showing features of natural killer cells and intraepithelial ILC1 (CD56+, NKp44+, CCR6+, CD127–, cytotoxicity, and IFNγ secretion), ILC3 (CD56+, NKp44+, IL‐23R+, CCR6+, RORγt+, and IL‐22 secretion), and intermediate ILC1–ILC3 phenotypes (IFNγ+IL‐22+). Viability of intestinal grafts may depend on the balance among proinflammatory and homeostatic roles of ILC subsets.
The distance to the cool T9 brown dwarf ULAS J003402.77-005206.7

Aims. We demonstrate the feasibility ofdetermining parallaxes for nearby objects withthe WideField Camera on the United Kingdom Infrared Telescope (UKIRT) using the UKIRT Infrared Deep Sky Survey as a first epoch. We determine physical parameters for ULAS J003402.77-005206.7, one of the coolest brown dwarfs currently known, using atmospheric and evolutionary models with the distance found here. Methods. Observations over the period 10/2005 to 07/2009 were pipeline processed at the Cambridge Astronomical Survey Unit and combined to produce a parallax and proper motion using standard procedures. Results. We determined π = 79.6 ±3. 8m as,μα = −20.0 ±3. 7m as/yr and μδ = −363.8 ±4. 3m as/yr for ULAS J003402.77-005206.7. Conclusions. We have made a direct parallax determination for one of the coolest objects outside of the solar system. The distance is consistent with a relatively young, 1−2 Gyr, low mass, 13−20 MJ, cool, 550−600 K, brown dwarf. We present a measurement of the radial velocity that is consistent with an age between 0.5 and 4.0 Gyr.
Detection of Calprotectin and Apoptotic Activity in the Colon of Marmosets with Chronic Diarrhea

ABSTRACT The common marmoset (Callithrix jacchus) is used as a non-human primate laboratory animal. Marmoset wasting syndrome (MWS) is a disease endemic to captive colonies, and the pathogenesis is unclear. In the present study, marmosets with chronic bloody high-viscosity diarrhea, which is a contributing factor to MWS, were evaluated, and inflammation in the colon was found. Calprotectin is a surrogate marker of intestinal inflammation and induces apoptosis. Marmosets with chronic diarrhea exhibited higher levels of fecal calprotectin. Histochemical analyses showed high expression of calprotectin in the extravascular neutrophils and apoptosis in the chronic colitis lesions. No internal microbiological diseases were identified. Although the cause of chronic colitis was not identified, the marmoset could be a useful model of inflammatory bowel disease.
Development of a FPGA Based Real-Time Power Analysis and Control for Distributed Generation Interface

Energy coming from renewable sources has become very important nowadays, mainly because of their negligible contribution to greenhouse gas generation. A problem that then arises is how to integrate these new sources into a traditional power grid, in such a manner as to maximize the efficiency and reliability of this new distributed generation (DG) system. The hardware to do that is generally a voltage source inverter (VSI) that supplies a common load, as in single-phase residential and commercial applications. The optimizing process requires, of course, the usual power analysis. This paper presents the development and the experimental evaluation of a power control system for a single-phase grid-connected VSI including the power analysis using as processor for the control implementation a field-programmable gate array (FPGA) circuit. New hardware structures of adaptive linear neural networks (ADALINE) allow the implementation of power control algorithms and have also permitted the real-time analysis of the high-order harmonics without increasing the implementation area of the FPGA circuit. These features are ideal for novel DG power electronics interfaces that could be used not only for active power dispatch but also for harmonics and reactive power compensation. Simulation and experimental results of the proposed fixed and variable frequency schemes are included to confirm their validity.