Miracle-dz/UniFAR-FTUs huggingface dataset:
Protease Inhibitor Coinfusion with Amyloid β-Protein Results in Enhanced Deposition and Toxicity in Rat Brain

Amyloid β-protein, Aβ, is normally produced in brain and is cleared by unknown mechanisms. In Alzheimer’s disease (AD), Aβ accumulates in plaque-like deposits and is implicated genetically in neurodegeneration. Here we investigate mechanisms for Aβ degradation and Aβ toxicity in vivo, focusing on the effects of Aβ40, which is the peptide that accumulates in apolipoprotein E4-associated AD. Chronic intraventricular infusion of Aβ40 into rat brain resulted in limited deposition and toxicity. Coinfusion of Aβ40 with the cysteine protease inhibitor leupeptin resulted in increased extracellular and intracellular Aβ immunoreactivity. Analysis of gliosis and TUNEL in neuron layers of the frontal and entorhinal cortex suggested that leupeptin exacerbated Aβ40 toxicity. This was supported further by the neuronal staining of cathepsin B in endosomes or lysosomes, colocalizing with intracellular Aβ immunoreactivity in pyknotic cells. Leupeptin plus Aβ40 caused limited but significant neuronal phospho-tau immunostaining in the entorhinal cortex. Intriguingly, Aβ40 plus leupeptin induced intracellular accumulation of the more toxic Aβ, Aβ42, in a small group of septal neurons. Leupeptin infusion previously has been reported to interfere with lysosomal proteolysis and to result in the accumulation of lipofuscin, dystrophic neurites, tau- and ubiquitin-positive inclusions, and structures resembling paired helical filaments. Coinfusion of Aβ40 with the serine protease inhibitor aprotinin also increased diffuse extracellular deposition but reduced astrocytosis and TUNEL and was not associated with intracellular Aβ staining. Collectively, these data suggest that an age or Alzheimer’s-related defect in lysosomal/endosomal function could promote Aβ deposition and DNA fragmentation in neurons and glia similar to that found in Alzheimer’s disease.
Investigations of valanimycin biosynthesis: Elucidation of the role of seryl-tRNA

The antibiotic valanimycin is a naturally occurring azoxy compound produced by Streptomyces viridifaciens MG456-hF10. Precursor incorporation experiments showed that valanimycin is derived from l-valine and l-serine via the intermediacy of isobutylamine and isobutylhydroxylamine. Enzymatic and genetic investigations led to the cloning and sequencing of the valanimycin biosynthetic gene cluster, which was found to contain 14 genes. A novel feature of the valanimycin biosynthetic gene cluster is the presence of a gene (vlmL) that encodes a class II seryl-tRNA synthetase. Previous studies suggested that the role of this enzyme is to provide seryl-tRNA for the valanimycin biosynthetic pathway. Here, we report the results of investigations to elucidate the role of seryl-tRNA in valanimycin biosynthesis. A combination of enzymatic and chemical studies has revealed that the VlmA protein encoded by the valanimycin biosynthetic gene cluster catalyzes the transfer of the seryl residue from seryl-tRNA to the hydroxyl group of isobutylhydroxylamine to produce the ester O-seryl-isobutylhydroxylamine. These findings provide an example of the involvement of an aminoacyl-tRNA in an antibiotic biosynthetic pathway.
Detection of Audio-Visual Integration Sites in Humans by Application of Electrophysiological Criteria to the BOLD Effect

Electrophysiological studies in nonhuman primates and other mammals have shown that sensory cues from different modalities that appear at the same time and in the same location can increase the firing rate of multisensory cells in the superior colliculus to a level exceeding that predicted by summing the responses to the unimodal inputs. In contrast, spatially disparate multisensory cues can induce a profound response depression. We have previously demonstrated using functional magnetic resonance imaging (fMRI) that similar indices of crossmodal facilitation and inhibition are detectable in human cortex when subjects listen to speech while viewing visually congruent and incongruent lip and mouth movements. Here, we have used fMRI to investigate whether similar BOLD signal changes are observable during the crossmodal integration of nonspeech auditory and visual stimuli, matched or mismatched solely on the basis of their temporal synchrony, and if so, whether these crossmodal effects occur in similar brain areas as those identified during the integration of audio-visual speech. Subjects were exposed to synchronous and asynchronous auditory (white noise bursts) and visual (B/W alternating checkerboard) stimuli and to each modality in isolation. Synchronous and asynchronous bimodal inputs produced superadditive BOLD response enhancement and response depression across a large network of polysensory areas. The most highly significant of these crossmodal gains and decrements were observed in the superior colliculi. Other regions exhibiting these crossmodal interactions included cortex within the superior temporal sulcus, intraparietal sulcus, insula, and several foci in the frontal lobe, including within the superior and ventromedial frontal gyri. These data demonstrate the efficacy of using an analytic approach informed by electrophysiology to identify multisensory integration sites in humans and suggest that the particular network of brain areas implicated in these crossmodal integrative processes are dependent on the nature of the correspondence between the different sensory inputs (e.g. space, time, and/or form).
Performance of concrete with blended binders in ammonium-sulphate solution

Concrete elements in agricultural, wastewater treatment, mining, and industrial applications can be vulnerable to chemical attack by ammonium-based solutions. In particular, ammonium sulfate (commonly used as a fertilizer) is extremely deleterious to concrete. This is due to its dual acid–sulfate action, which may disintegrate the hydrated cement paste to various levels based on the prevailing exposure conditions and key mixture design parameters of concrete. The aim of this study was to investigate the response, in terms of physico-mechanical and microstructural features, of concrete comprising different types of cement (general use [GU] or Portland limestone cement [PLC]) with various combinations of supplementary cementitious materials (SCMs: fly ash, silica fume, and nanosilica) to a severe ammonium sulfate exposure. The study comprised 12 months of immersing test specimens in 5% ammonium sulfate solutions with a pH level of 6.0–8.0. The results revealed that the type of binder along with the dosage and nature of SCMs dictated different modes and levels of deterioration, and consequently the physico-mechanical trends of concrete were characterized by softening with (single binders) or without (blended binders) significant expansion. PLC may slightly improve the resistance of concrete to ammonium sulfate attack, whereas among the blended binders tested, binary binders comprising 5% silica fume, 5% nanosilica, or 30% fly ash improved the resistance of concrete to this type of chemical attack.
Red Wine Polyphenols Enhance Endothelial Nitric Oxide Synthase Expression and Subsequent Nitric Oxide Release From Endothelial Cells

Background—Population-based studies suggest a reduced incidence of morbidity and mortality from coronary heart disease caused by moderate and regular consumption of red wine. Endothelial nitric oxide (NO) is a pivotal vasoprotective molecule. This study examines the influence of red wine polyphenols on the regulation of endothelial nitric oxide synthase (eNOS) expression and subsequent NO synthesis, focusing on the putative long-lasting antiatherosclerotic effects of red wine. Methods and Results—Treatment (20 hours) of human umbilical vein endothelial cells (HUVECs) and of the HUVEC-derived cell line EA.hy926 with a alcohol-free red wine polyphenol extract (RWPE) led to a concentration-dependent (100 to 600 &mgr;g/mL), significant increase in NO release (up to 3.0-fold/HUVEC and 2.0-fold/EA.hy926) as shown by use of the fluorescent probe DAF-2. This effect was corroborated by the [14C]l-arginine/l-citrulline conversion assay in intact EA.hy926 cells. RWPE (20 hours, 100 to 600 &mgr;g/mL) also significantly increased eNOS protein levels up to 2.1-fold. Furthermore, we found an increased human eNOS promotor activity (up to 2-fold) in response to red wine polyphenols (18 hours, 100 to 600 &mgr;g/mL), as demonstrated by a luciferase reporter gene assay. Conclusion—We provide conclusive data showing for the first time that a RWPE increases eNOS expression and subsequent endothelial NO release. Increased active eNOS levels may antagonize the development of endothelial dysfunction and atherosclerosis, a hypothesis that supports the view that red wine indeed may have long-term protective cardiovascular properties mediated by its polyphenols.
Burden of informal carers of mentally infirm eldery in Lancashire.

OBJECTIVES To compare the burden of supporting demented and non-demented mentally infirm elders in an English community; determine the prevalence of emotional distress in carers and to investigate the relationship between carer well being and duration of care giving. DESIGN Cross-sectional study of informal carers of the elderly referred to a psychogeriatric service, using a questionnaire investigating carer socio-demography, carer-dependant interpersonal relationship in relation to care giving and care-recipient dependency needs using a modified version of the CADI; and, the 28-item GHQ. SETTING Lancashire communities of Fleetwood, Thornton-Cleveleys, Poulton- Le-Fylde and Over-Wyre. RESULTS Ninety one (72%) carers of the elderly mentally infirm participated in the study. Carers (n = 48) of the demented experienced significantly more burden, including psychological and physical health problems than carers (n = 43) of the non-demented (P = 0.001). The prevalence of emotional distress in all carers was 42% (dementia supporters = 56%, non-dementia supporters = 26%). Emotional distress in supporters was directly related to the degree of difficulties (particularly lack of private time, loss of control in caregiving tasks, patient behavioural problems) experienced in care giving, and, the degree of patient dependency needs. Carer/patient interpersonal relationship tended to worsen as care giving progressed; however, no significant association was established between duration of care and emotional distress in carers. Out of 51 carers receiving respite admission services, six (12%) considered such admissions as additional burden. CONCLUSIONS Carer burden, including psychological and physical health concerns, was comparatively greater in carers of the demented than in carers of the non-demented. Respite care services although beneficial to most care givers, may constitute further burden to some. Factors accounting for these observations are explained. To ameliorate carer burden, measures enabling greateravailability of private time, and, improving care giving skills, should be encouraged.
The Morbidity of Oral Mucosal Lesions in an Adult Swedish Population

Objectives: To study the severity of symptoms and estimate the prevalence of oral mucosal lesions in a non-referral adult Swedish population, as registered by general dental practitioners. This study also aims to evaluate the possibi-lity of dental practitioners collecting large quantities of reliable and accurate clinical data on oral mucosal lesions. Study Design: Data from 6,448 adult Swedish patients were collected by general dental practitioners using a standardized registration method. A correlation analysis between a group with oral mucosal lesions and a control group, with no oral mucosal lesions, was performed for various parameters such as symptoms from the oral mucosa, systemic diseases, medication, allergy history, tobacco habits and the patient’s own assessment of their general health. In addition, clinical photos were taken of all oral mucosal lesions in order to determine the degree of agreement between the diagnoses made by general dental practitioners and those made by oral medicine specialists. Results: A total of 950 patients (14.7%) presented with some type of oral mucosal lesion and of these, 141 patients (14.8%) reported subjective symptoms. On a visual analogue scale, 43 patients (4.5%) scored their symptoms <30, 65 patients (6.8%) scored their symptoms ? 30, and 28 patients (2.6%) scored their symptoms ? 60. The most debilitating condition was aphthous stomatitis and the most common oral mucosal lesion was snuff dipper’s lesion (4.8%), followed by lichenoid lesions (2.4%) and geographic tongue (2.2%). There was agreement between the oral medicine specialists and the general practitioners over the diagnosis of oral mucosal lesions on the basis of a clinical photograph in 85% of the cases (n=803). Conclusions: Nearly 15% of the patients with oral mucosal lesions reported symptoms. General practitioners could contribute significantly to the collection of large quantities of reliable and accurate clinical data, although there is a risk that the prevalence of oral mucosal lesions may be underestimated. Key words:Epidemiology, oral mucosal lesions, oral medicine, examiner reliability.
Spotty: Imaging sonification based on spot-mapping and tonal volume

A basic question at image sonification is the image segmentation. A cognitive model of visual processing in a greater degree could define possible ways of sound mapping. For instance, the scanpath theory suggests that a top-down internal cognitive model, of what we see, drives the sequences of rapid eye movements and fixations or glances that so efficiently travel over scene or picture of interest. The scanpath theory may be applied at sonification of visual image. But it is necessary to solve, what is more important in each stage of the image recognition process: the scan trajectory or the optical characteristics of its extreme positions? That is to say, what is dominant scanpath or the spot of glance? I hope a solution of these questions will allow to develop new tools for VR applications as well as to continue designing of visualization system for blind people on a basis of blind-eye tracking.
Classifying paragraph types using linguistic features: Is paragraph positioning important?

This study examines the potential for computational tools and human raters to classify paragraphs based on positioning. In this study, a corpus of 182 paragraphs was collected from student, argumentative essays. The paragraphs selected were initial, middle, and final paragraphs and their positioning related to introductory, body, and concluding paragraphs. The paragraphs were analyzed by the computational tool Coh-Metrix on a variety of linguistic features with correlates to textual cohesion and lexical sophistication and then modeled using statistical techniques. The paragraphs were also classified by human raters based on paragraph positioning. The performance of the reported model was well above chance and reported an accuracy of classification that was similar to human judgments of paragraph type (66% accuracy for human versus 65% accuracy for our model). The model’s accuracy increased when longer paragraphs that provided more linguistic coverage and paragraphs judged by human raters to be of higher quality were examined. The findings support the notions that paragraph types contain specific linguistic features that allow them to be distinguished from one another. The finding reported in this study should prove beneficial in classroom writing instruction and in automated writing assessment.
Maternal breastfeeding self-efficacy and the breastfeeding behaviors of newborns in the practice of exclusive breastfeeding.

OBJECTIVES To explore the maternal breastfeeding self-efficacy of Chinese women, the breastfeeding behaviors of newborns, and the relationship with breastfeeding outcomes at 6 weeks postpartum. DESIGN Descriptive correlation study. SETTING Postnatal ward of a regional maternity hospital PARTICIPANTS All postnatal Chinese women who were admitted from mid-February 2010 to mid-March 2010 with the intention of breastfeeding. METHODS The Infant Breastfeeding Assessment Tool (IBFAT) was used to assess neonatal breastfeeding behaviors, and a modified Chinese version of the Breastfeeding Self-Efficacy Scale-Short Form (MBSES-SF) was used to examine the breastfeeding self-efficacy of mothers. RESULTS A total of 199 postnatal women were recruited. At 6 weeks postpartum, 85 (42.7%) infants were bottle-fed, 66 (33.2%) were complementary breastfed, and 48 (24.1%) were exclusively breastfed. The significant contributing factors for exclusive breastfeeding were women who planned to breastfeed for at least 6 months (odds ratio [OR] = 5.537, 95% confidence interval [CI] [2.430, 12.619], p ≤ 0.001), women with a high level of breastfeeding self-efficacy (OR =, 7.776, 95% CI [2.546, 23.748], p ≤ 0.001), and those women whose infants had high-IBFAT scores (OR = 2.381, 95% CI [1.019, 5.562], p = .045). CONCLUSIONS Maternal breastfeeding confidence and newborn breastfeeding behavior are strong predictors of breastfeeding duration as well as exclusivity. Health care professionals should monitor the breastfeeding behavior of newborns and not only provide mothers with the factual information on breastfeeding but help also them to develop maternal confidence in breastfeeding before they are discharged.
The ttpC Gene Is Contained in Two of Three TonB Systems in the Human Pathogen Vibrio vulnificus, but Only One Is Active in Iron Transport and Virulence

ABSTRACT The TonB system of proteins is required for the energy-dependent active transport of iron-bound substrates across the outer membrane of Gram-negative bacteria. We have identified three TonB systems within the human pathogen Vibrio vulnificus. The TonB1 system contains the TonB1, ExbD1, and ExbB1 proteins, whereas both the TtpC2-TonB2 and TtpC3-TonB3 systems contain an additional fourth protein, TtpC. Here we report that TtpC3, although highly related to TtpC2, is inactive in iron transport, whereas TtpC2 is essential for the function of the TtpC2-TonB2 system in V. vulnificus. This protein, together with TonB2, is absolutely required for both the uptake of endogenously produced iron-bound siderophores as well as siderophores produced from other organisms. Through complementation we show that V. vulnificus is capable of using different TtpC2 proteins from other Vibrio species to drive the uptake of multiple siderophores. We have also determined that aerobactin, a common bacterial siderophore involved in virulence of enteric bacteria, can only be brought into the cell using the TtpC2-TonB2 system, indicating an important evolutionary adaptation of TtpC2 and TonB2. Furthermore, in the absence of TonB1, TtpC2 is essential for a fully virulent phenotype as demonstrated using 50% lethal dose (LD50) experiments in mice.
Performance and capacity-based measures of locomotion, compared to impairment-based measures, best predicted participation in individuals with hemiparesis due to stroke

Abstract Purpose: To determine the potential predictors of participation of individuals with post-stroke hemiparesis, taking into account modifiable variables of impairments, activity limitations, and environmental factors. Methods: One hundred and nine individuals (58 ± 12 years; 64 men) participated in this study. Outcomes included measures of impairments (depressive symptoms: Geriatric Depression Scale and motor-based impairments: finger-to-nose test, lower extremity (LE) motor coordination test, and handgrip strength, isometric strength of the LE muscles), activity (capacity: 10-meter walking speed test and Test d'Évaluation des Membres Supérieurs de Personnes Agées; performance: locomotion and manual abilities; environmental factors (Measure of the Quality of the Environment); and participation: Assessment of Life Habits (LIFE-H 3.1 Brazil)). Results: Regression analyses revealed that the explanatory variables accounted for 59% and 49% of the variance in the LIFE-H 3.1 Brazil daily activity and social role sub-scales, respectively. Locomotion performance (R2 = 39%; p < 0.0001) and walking speed (R2 = 32%; p < 0.0001) were the best predictors of the LIFE-H 3.1 Brazil daily activity and social role sub-scales, respectively. Depressive symptoms were the only impairments, which were retained in both models. Conclusions: Performance and capacity-based measures of locomotion showed to be the best predictors of participation. Additionally, depressive symptoms should not be underlooked. Implications for Rehabilitation Activity-related measures of locomotion showed to be the main predictors of participation in individuals with post-stroke hemiparesis, as assessed by the daily activity and social role sub-scales of the LIFE-H 3.1. The daily activity model was best predicted by measures of performance, whereas the social role sub-scale, by measures of capacity. Although small, the impact of depressive symptoms on participation should not be underlooked. Locomotion appeared to be essential for participation and increases in walking speed and locomotion ability should be the main goals for both professionals and individuals, when the aim is to increase participation.
Confirmation of Indandione Rodenticide Toxicoses by Mass Spectrometry/Mass Spectrometry

Mass spectrometry/mass spectrometry (MS/MS) with collision-activated dissociation (CAD) was utilized to unequivocally distinguish 1,3-indandione rodenticides in 2 cases of anticoagulant toxicosis. Anecdotal evidence provided by the veterinarian in a case involving feedlot cows and physical evidence at the site of occurrence in a similar case involving lambs strongly implicated diphenadione (diphacinone; DP) in both instances. However, high performance liquid chromatography indicated chlorophacinone (CP), not DP, was present in the blood samples obtained from both cows and lambs. Intact 1,3-indandiones exhibit poor gas chromatographic properties, so procedures were developed for analysis by MS/MS using a direct exposure probe for sample introduction. The EI mass spectra of DP and CP contained a base peak at m/z 173, with molecular ions (M+) at m/z 340 and m/z 374 (Cl isotope cluster), respectively. Corresponding MS/MS CAD parent ion spectra of m/z 173 showed an ion of m/z 340 for DP and 374 (Cl cluster) for CP. CAD analysis of the blood extracts showed a parent ion scan of m/z 173 identical to that of CP, with the m/z 374 (Cl cluster). (Additional evidence was obtained by MS/MS examination of the CAD daughter ion spectrum of m/z 374.) Blood extracts from the affected animals revealed CAD daughter ion spectra for m/z 374 identical to that of reference CP. Positive confirmation of CP in both cases led to identification of the source of the toxicant and prevention of further animal exposures.