Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Exoribonucleases Act Sequentially to Process Mature 3′-Ends of atp9 mRNAs in Arabidopsis Mitochondria*

In plant mitochondria, transcription proceeds well beyond the region that will become mature 3′ extremities of mRNAs, and the mechanisms of 3′ maturation are largely unknown. Here, we show the involvement of two exoribonucleases, AtmtPNPase and AtmtRNaseII, in the 3′ processing of atp9 mRNAs in Arabidopsis thaliana mitochondria. Down-regulation of AtmtPNPase results in the accumulation of pretranscripts of several times the size of mature atp9 mRNAs, indicating that 3′ processing of these transcripts is performed mainly exonucleolytically by AtmtPNPase. This enzyme is however not sufficient to completely process atp9 mRNAs, because with down-regulation of another mitochondrial exoribonuclease, AtmtRNaseII, about half of atp9 transcripts exhibit short 3′ nucleotide extensions compared with mature mRNAs. These short extensions can be efficiently removed by AtmtRNaseII in vitro. Taken together, these results show that 3′ processing of atp9 mRNAs in Arabidopsis mitochondria is, at least, a two-step phenomenon. First, AtmtPNPase is involved in removing 3′ extensions that may reach several kilobases. Second, AtmtRNaseII degrades short nucleotidic extensions to generate the mature 3′-ends.
Increased [3H]D‐aspartate release and changes in glutamate receptor expression in the hippocampus of the mnd mouse

Neuronal ceroid lipofuscinoses (NCLs) are a group of hereditary childhood diseases characterized mainly by lipopigment accumulation and a multisystemic pattern of symptoms including mental retardation, seizures, motor impairment, and blindness. The mnd mouse, carrying a mutation in the Cln8 gene, has been proposed as a model of epilepsy with mental retardation (EPMR, ornorthern epilepsy). We recently showed neuronal hyperexcitability and seizure hypersusceptibility in mnd mice. To elucidate the cellular mechanisms related to hippocampal hyperexcitability, the glutamatergic transmission and the expression of postsynaptic glutamate receptors were investigated in hippocampus. A significant increase in either spontaneous or KCl‐stimulated overflow of [3H]D‐aspartate was found in mnd mice compared with controls. This increase was maintained after DL‐threo‐β‐benzyloxyaspartic acid (TBOA) treatment, suggesting a nonrelevant role for transporter‐mediated release and supporting the involvement of exocytotic [3H]D‐aspartate release. Accordingly, Ca2+‐dependent overflow induced by ionomycin was also increased in mnd mice. Levels of glutamate 1–3 AMPA receptor subunits were increased, and levels of the NR2A NMDA receptor subunit were decreased in the hippocampus of mnd mice, suggesting an adaptive response to glutamate overstimulation. © 2012 Wiley Periodicals, Inc.
The use of CT in dementia

ABSTRACT Neuroimaging has become part of the required investigations when assessing a patient with dementia. In this brief paper, we summarize the role of computed tomography (CT) in the routine work-up in dementia and provide some information about the role of the CT scan in the field of dementia research. Although CT is far less sensitive than magnetic resonance imaging (MRI) in detecting changes associated with cognitive impairment, it may still have a role in this regard. This role is mainly that of detecting secondary, sometimes treatable causes of cognitive impairment, such as intracranial masses. In this sense, CT should be seen as a first-line tool. Possible advantages of CT are lower cost; shorter acquisition time, making it more adaptable to patients with poor compliance; and the possibility that it can be performed in patients with metal devices, such as a pacemaker. The role of CT in the field of dementia research is very restricted in comparison to that of MRI, and is limited to the structural assessment of vascular lesions, and to a lesser extent, to that of degenerative changes, particularly when using specific slicing.
Potassium Channel Blockers Have Minimal Effect on Repolarization of Spontaneous Action Potentials in Rat Pituitary Lactotropes

Patch-clamp techniques were used in primary cultures of rat lactotropes and the rat pituitary clonal cell line GH3 to determine the population characteristics of spontaneous action potentials and the nature of the currents responsible for repolarization of spontaneous action potentials. Spontaneous action potentials were observed in 75% of lactotropes (74/99) and 80% of GH3 cells (42/51). Lactotropes exhibited broad and shallow action potentials (average duration 460 ms, peak –17 mV, slope of upstroke 0.5 mV/ms) compared to the GH3 cells which displayed narrow and tall action potentials (average duration 177 ms, peak –10 mV, slope of upstroke 1.6 mV/ms). Blockers of potassium currents were used to determine the role of specific potassium currents in the repolarization process. Spontaneous action potentials in lactotropes were largely unaffected by 4-aminopyridine (4AP), charybdotoxin, and apamin. Tetraethylammonium (TEA) caused only an small increase in peak amplitude and, in a subset of cells, a small increase in duration. In contrast, in GH3 cells, TEA, 4AP, charybdotoxin, and apamin all caused a significant increase in duration, while TEA and charybdotoxin also caused an increase in peak amplitude. Further, apamin caused a positive shift in the afterhyperpolarization voltage. In lactotropes, strong buffering of intracellular calcium with calcium chelators (EGTA or BAPTA) caused a profound increase in action potential duration. Thus, repolarization of action potentials in lactotropes is a calcium-dependent process, but unlike GH3 cells, is not mediated by calcium-dependent potassium currents, nor is it strongly influenced by voltage-dependent potassium currents.
Fundamental concepts of using water activity probes to assess transformer insulation water content

The water concentration in transformer paper insulation must be monitored because, if it becomes too high, the paper insulation will age rapidly [1]-[4] and the transformer may fail on overload [5]-[9]. A failure can occur on overload if the temperature of the paper rises sufficiently to cause evolution of water bubbles. If these bubbles cause dielectric failure of the oil gap, the transformer may fail catastrophically. Paper insulation becomes brittle as it ages, and eventually becomes too brittle to act as an effective insulator. Oxygen increases the aging rate because the acids created by chemical reactions occurring in the oil, paper, and oxygen react further with water [10]-[12]. A study of the thermal aging of Kraft paper found that wet oxygenated paper degrades 40 times faster than the same paper heated in a dry oxygen-free environment [4]. The paper within a transformer is likely to degrade fastest at the top of the winding, where it is hottest [13]. Since the water concentration in the paper significantly influences its aging, it is important that the water concentration be measured accurately at the top of the winding.
Natural History of Brain Lesions in Extremely Preterm Infants Studied With Serial Magnetic Resonance Imaging From Birth and Neurodevelopmental Assessment

OBJECTIVES. The aim was to survey the range of cerebral injury and abnormalities of cerebral development in infants born between 23 and 30 weeks’ gestation using serial MRI scans of the brain from birth, and to correlate those findings with neurodevelopmental outcome after 18 months corrected age. METHODS. Between January 1997 and November 2000, consecutive infants born at <30 weeks’ gestational age underwent serial MRI brain scans from birth until term-equivalent age. Infants were monitored after 18 months of age, corrected for prematurity, with the Griffiths Mental Development Scales and neurologic assessment. RESULTS. A total of 327 MRI scans were obtained from 119 surviving infants born at 23 to 30 weeks of gestation. Four infants had major destructive brain lesions, and tissue loss was seen at term for the 2 survivors. Fifty-one infants had early hemorrhage; 50% of infants with term scans after intraventricular hemorrhage had ventricular dilation. Twenty-six infants had punctate white matter lesions on early scans; these persisted for 33% of infants assessed at term. Early scans showed cerebellar hemorrhagic lesions for 8 infants and basal ganglia abnormalities for 17. At term, 53% of infants without previous hemorrhage had ventricular dilation and 80% of infants had diffuse excessive high signal intensity within the white matter on T2-weighted scans. Complete follow-up data were available for 66% of infants. Adverse outcomes were associated with major destructive lesions, diffuse excessive high signal intensity within the white matter, cerebellar hemorrhage, and ventricular dilation after intraventricular hemorrhage but not with punctate white matter lesions, hemorrhage, or ventricular dilation without intraventricular hemorrhage. CONCLUSIONS. Diffuse white matter abnormalities and post–hemorrhagic ventricular dilation are common at term and seem to correlate with reduced developmental quotients. Early lesions, except for cerebellar hemorrhage and major destructive lesions, do not show clear relationships with outcomes.
he Diet – Heart Hypothesis : A Critique ylvan

The low-fat “diet–heart hypothesis” has been controversial for nearly 100 years. The low-fat–high-carbohydrate diet, promulgated vigorously by the National Cholesterol Education Program, National Institutes of Health, and American Heart Association since the Lipid Research Clinics-Primary Prevention Program in 1984, and earlier by the U.S. Department of Agriculture food pyramid, may well have played an unintended role in the current epidemics of obesity, lipid abnormalities, type II diabetes, and metabolic syndromes. This diet can no longer be defended by appeal to the authority of prestigious medical organizations or by rejecting clinical experience and a growing medical literature suggesting that the much-maligned low-carbohydrate–high-protein diet may have a salutary effect on the epidemics in question. (J Am Coll Cardiol 2004;43:731–3) © 2004 by the American College of Cardiology Foundation
Stroke in the young in Israel. Incidence and outcomes.

BACKGROUND AND PURPOSE Data on stroke in the young in Israel are fragmentary. To obtain an overall perspective and to assess the nature and magnitude of the problem, a study was conducted on stroke occurrence in the young population during 1 year. Incidence and outcomes are reported in this communication. METHODS We conducted a prospective ascertainment of first stroke in all permanent residents of Israel aged 17 to 49 years who were referred to all acute-care hospitals in the country or died before reaching them. RESULTS We identified 253 first stroke victims in the studied population; 62.8% were male. The age- and sex-adjusted incidence rate for all types of stroke was 10.36/100 000 per year (males, 13.00; females, 7.71). The majority of strokes (80.6%) were cerebral infarctions, with 9.9% intracerebral hemorrhages, 7.9% subarachnoid hemorrhages, and 1.6% strokes of unspecified type. The case-fatality rate for all types of stroke was 9.9% (mortality within the first 4 weeks after the event, on average 6 days). The survival rate was 95% for cerebral infarctions, 64% for intracerebral hemorrhages, and 80% for subarachnoid hemorrhages; 86.7% of all survivors remained with an impairment resulting in a disability. CONCLUSIONS Incidence rates were similar to those reported from developed Western countries. The case-fatality rate of 9.9% and the considerable percentage of survivors with a disability in a population at the beginning of their family, professional, and social lives indicate the magnitude of the problem.
Diurnal IOP control with bimatoprost versus latanoprost in exfoliative glaucoma: a crossover, observer-masked, three-centre study

Aim: To evaluate the diurnal intraocular pressure (IOP) control and safety of bimatoprost versus latanoprost in exfoliative glaucoma (XFG). Methods: One eye of 129 consecutive patients with XFG (mean (SD) age 66.5 (8.3) years) was included in this prospective, observer-masked, three-centre, crossover comparison. After a 4–6 week medicine-free period patients were randomised to bimatoprost or latanoprost monotherapy for 3 months. Patients were then switched to the opposite treatment for another 3 months. At the end of the washout and the treatment periods diurnal IOP was measured at 0800, 1300, and 1800. Results: At baseline the IOP (mean (SD)) was 28.0 (4.0), 26.9 (3.6), and 25.9 (3.6) mm Hg, at the three time points, respectively. Both treatments significantly reduced mean diurnal IOP at month 3. Mean diurnal IOP was 26.9 (3.5) mm Hg at baseline, 17.6 (3.3) mm Hg with bimatoprost, and 18.6 (3.6) mm Hg with latanoprost (p<0.0001). Furthermore, lower IOP values were obtained with bimatoprost at all time points (17.9 (3.4), 17.3 (3.3), and 17.6 (3.5) mm Hg, respectively) compared with latanoprost (18.7 (3.6), 18.5 (3.6), and 18.6 (4.1) mm Hg, respectively). The corresponding mean differences (0.8, 1.1, and 1.0 mm Hg, respectively) were all significant (p<0.001 for each comparison). Significantly more patients with XFG obtained a target diurnal IOP <17 mm Hg with bimatoprost than with latanoprost, 55/123 (45%) v 34/123 (28%); (p = 0.001), and significantly fewer patients were non-responders with bimatoprost than with latanoprost (5 v 13, p = 0.021). More patients reported at least one adverse event with bimatoprost than with latanoprost (58 v 41 at 3 months; p = 0.0003). Conclusion: This crossover study suggests that better diurnal IOP control is obtained with bimatoprost than with latanoprost in patients with XFG.
Attachment theory in child welfare exploring the integration of attachment theory in child welfare practice

This research thesis is a small exploration of attachment theory in child welfare practice. The researcher investigated the extent of knowledge that child protection workers had of attachment theory and the extent to which they integrated attachment theory into child welfare practice. A purposive non-probability sample was used to recruit General Authority child welfare workers in Manitoba. Five workers participated in the exploratory qualitative descriptive research study. Participants responded to a demographic survey investigating their education, training, years of service and the participants provided a brief description of attachment theory. Participants also reviewed vignettes and responded to semi-structured interview scripts eliciting practice information related to the vignettes. The data elicited was analyzed using content analysis. The degree of exposure to attachment theory, opportunities to engage in theory informed practice, and external and internal agency pressures were observed to influence theory integration into child welfare practice. Participants acknowledged the attachment theory concepts of transmission of parenting behaviours and attachment strategies through relationships. Participants considered the therapeutic capacity of relational and attachment focused interventions to bring about change to maladaptive parenting behaviours.
Corporate reporting and accounting for externalities

Externalities comprise economic, social and/or environmental impacts arising from the activities of an entity that are borne by others, at least in the short term. As they do not feedback directly into immediate financial consequences for the entity, they tend to be outside the remit of financial reporting. A dispersed academic accounting literature on externalities has hitherto developed separately from concerns about what information is appropriate to report on corporate performance. This paper develops insights into accounting for, and reporting of, externalities that are intended to improve the use of externalities information in breaking down silos between the traditionally discrete domains of financial reporting and sustainability reporting, and between silos within sustainability reporting. Challenges in such use of externalities information are explored, including difficulties inherent in the quantification of externalities. The paper also highlights ways in which externalities can progressively become internalised, thereby bringing them more readily within the domain of economically focused financial reporting practices. An agenda for further research to help enhance the accounting for, and reporting of, externalities is also proposed.
THE MOLECULAR GENETICS OF ANTITHROMBIN DEFICIENCY

Antithrombin is the major proteinase inhibitor of thrombin and other blood coagulation proteinases. Antithrombin has two functional domains, a heparin binding site and a reactive centre (that complexes and inactivates the proteinase). Its deficiency results in an increased risk of venous thromboembolism. Appreciable progress has been made in recent years in understanding the structure and function of this protein, the genetic cause of inherited deficiency and its clinical consequence. The structure of antithrombin is now considered in terms of the models derived from X-ray crystallography, which have provided explanations for the function of its heparin interaction site and of its reactive loop. The structural organization of the antithrombin gene has been defined and numerous mutations have been identified that are responsible for antithrombin deficiency: these may reduce the level of the protein (Type I deficiency), alter the function of the protein (Type II deficiency, altering heparin binding or reactive sites), or even have multiple or 'pleiotropic effects' (Type II deficiency, altering both functional domains and the level of protein).
Physician Attitudes regarding Prostaglandin Treatment for Glaucoma in the United States and Europe

Purpose To evaluate physician use of prostaglandins (latanoprost, travoprost, and bimatoprost) in the United States (US) and Europe (EU). Methods One thousand multiple-choice surveys were distributed via e-mail in the US and EU. Results The authors received 71 responses (US 40 [8%] and EU 31 [6%]). Physicians preferred prostaglandin monotherapy (US 39 [98%] and EU 22 [71%], p=0.003), usually latanoprost (US 32 [80%] and EU 22 [71%], p=0.45). When more efficacy was required, US physicians would typically switch (23 [58%]) and EU physicians would add therapy (22 [71%], p=0.007). In both continents 45% of respondents stated bimatoprost was more efficacious. Conclusions US and EU physicians prefer prostaglandin monotherapy, most commonly latanoprost. Bimatoprost is often perceived as more effective, but having a higher incidence of conjunctival hyperemia.
Plakophilin 2A is the dominant isoform in human heart tissue: consequences for the genetic screening of arrhythmogenic right ventricular cardiomyopathy

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease in which mutations affecting Plakophilin-2 (PKP2) are the most frequently detected. However, pathogenicity of variants is not always fully determined. PKP2 encodes two isoforms, the longest (PKP2b) includes the alternatively spliced exon 6, which is routinely screened for molecular diagnosis, despite the absence of data on cardiac expression of PKP2 isoforms. Objective To examine the pathogenicity of PKP2 exon 6 mutations by focusing on a missense variant located in this exon. Methods and results The PKP2 heterozygous p.Arg490Trp variant was identified in two unrelated ARVC probands (absent from 470 controls). In silico analysis suggested that PKP2 exon 6 is an Alu-derived sequence with very low expression level. PKP2a mRNA, which does not include the sequence encoded by exon 6, was the dominant isoform transcribed; at western blot analysis PKP2A was the only clearly detectable isoform in all human heart samples analysed (from six different controls and the proband). Moreover, in the proband's sample, p.Arg490Trp was not associated with aberrant exon 6 splicing or mutant mRNA downregulation. Finally, a heterozygous missense variant (p.Glu2343Lys) in Desmoplakin was identified in this proband and is likely to be the disease-causing mutation. Conclusion PKP2A was shown to be the major isoform expressed in human heart tissue and PKP2B protein was undetectable. The results strongly suggest that p.Arg490Trp and other variants located in PKP2 exon 6 may not be disease causing. Variant splicing also has important consequences for the interpretation of mutation analysis and genetic counselling in ARVC and other hereditary cardiac diseases.
Investigating protein isoforms via proteomics: A feasibility study

Alternative splicing (AS) and processing of pre‐messenger RNAs explains the discrepancy between the number of genes and proteome complexity in multicellular eukaryotic organisms. However, relatively few alternative protein isoforms have been experimentally identified, particularly at the protein level. In this study, we assess the ability of proteomics to inform on differently spliced protein isoforms in human and four other model eukaryotes. The number of Ensembl‐annotated genes for which proteomic data exists that informs on AS exceeds 33% of the alternately spliced genes in the human and worm genomes. Examining AS in chicken via proteomics for the first time, we find support for over 600 AS genes. However, although peptide identifications support only a small fraction of alternative protein isoforms that are annotated in Ensembl, many more variants are amenable to proteomic identification. There remains a sizeable gap between these existing identifications (10–52% of AS genes) and those that are theoretically feasible (90–99%). We also compare annotations between Swiss‐Prot and Ensembl, recommending use of both to maximize coverage of AS. We propose that targeted proteomic experiments using selected reactions and standards are essential to uncover further alternative isoforms and discuss the issues surrounding these strategies.
Ultrawideband Underwater Acoustic Communication Channels

Traditional channel models for communications research are designed for narrowband systems. Underwater acoustic communication systems use a bandwidth that is not small compared with the center frequency of the signal and qualify as ultrawideband (UWB) in a relative sense. In this paper, measurements and analysis of acoustic propagation effects demonstrate the shortcomings of narrowband channel models. These effects are frequency-dependent fluctuation rates and frequency-dependent attenuation, where the frequency dependence of the attenuation differs between paths. This frequency selectivity of the medium violates the assumption of uncorrelated taps and requires a UWB channel model. It is also shown that correlative channel sounders preserve wideband properties, which renders them suitable for UWB channel simulation based on the principle of direct replay.