Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron‐enriched oligodendrocytes: A reexamination of their spatial distribution

Previous histochemical studies of iron in the brain demonstrated iron enrichment in oligodendrocytes, but the iron‐enriched oligodendrocytes had a spatially restricted distribution that excluded major white matter tracts. In this study we used techniques designed to permeabilize tissue, combined with iron histochemistry, and we observed iron‐enriched oligodendrocytes in regions previously thought to lack such cells. Our data suggest that most, if not all, oligodendrocytes are enriched in iron. We suggest that iron functions in the formation and/or maintenance of the myelin sheet and may play a role in the pathology of myelin diseases.
The Deep Versus the Shallow: Effects of Co-Speech Gestures in Learning From Discourse

This study concerned the role of gestures that accompany discourse in deep learning processes. We assumed that co-speech gestures favor the construction of a complete mental representation of the discourse content, and we tested the predictions that a discourse accompanied by gestures, as compared with a discourse not accompanied by gestures, should result in better recollection of conceptual information, a greater number of discourse-based inferences drawn from the information explicitly stated in the discourse, and poorer recognition of verbatim of the discourse. The results of three experiments confirmed these predictions.
Flow-induced wall mechanics of patient-specific aneurysmal cerebral arteries: Nonlinear isotropic versus anisotropic wall stress

Fluid–structure interaction simulations of three patient-specific models of cerebral aneurysms were carried out with the objective of quantifying the effects of non-Newtonian blood flow and the vessel mechanical behavior on the time-dependent fluid shear and normal stresses, and structural stress and stretch. The average wall shear stress at peak systole was found to be approximately one order of magnitude smaller than the shear stresses in the proximal communicating arteries, regardless of the shape or size of the aneurysms. Spatial distributions of oscillatory shear index were consistent with the reciprocal of wall shear stress distributions at peak systole for all aneurysm geometries, demonstrating that oscillatory shear index correlates inversely with wall shear at this time point in the cardiac cycle. An aneurysm wall modeled with an isotropic material resulted in an underestimation of both the maximum principal stress and stretch, compared to the anisotropic material model. For the three aneurysm geometries, anisotropic peak wall stresses were approximately 50% higher than for an isotropic material. Regardless of the constitutive material, the maximum stresses were consistently located at the aneurysm neck; stresses in the dome were 30% of those in the neck.
Chloroquine enhances the cytotoxicity of topotecan by inhibiting autophagy in lung cancer cells

Although the anti-malaria drug chloroquine (CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials, the potential mechanisms underlying this enhancement are still unclear. Here, we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan (TPT). The lung cancer cell line A549 was treated with TPT alone or TPT combined with CQ at non-cytotoxic concentrations. Cell viability was assessed using the MTT assay. The percentage of apoptotic cells and the presence of a side population of cells were both determined by flow Cytometry. Autophagy and the expression of Bcl-2 family proteins were examined by Western blotting. The accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles were examined by confocal microscopy. CQ sensitized A549 cells to TPT and enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion. CQ inhibited TPT-induced autophagy, which modified the cytotoxicity of TPT. However, CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did not increase lysosomal permeability. This study showed that CQ at non-cytotoxic concentrations potentiated the cytotoxicity of TPT by interfering with autophagy, implying that CQ has significant potential as a chemotherapeutic enhancer.
Preclinical Retinal Neurodegeneration in a Model of Multiple Sclerosis

Neurodegeneration plays a major role in multiple sclerosis (MS), in which it is thought to be the main determinant of permanent disability. However, the relationship between the immune response and the onset of neurodegeneration is still a matter of debate. Moreover, recent findings in MS patients raised the question of whether primary neurodegenerative changes can occur in the retina independent of optic nerve inflammation. Using a rat model of MS that frequently leads to optic neuritis, we have investigated the interconnection between neurodegenerative and inflammatory changes in the retina and the optic nerves with special focus on preclinical disease stages. We report that, before manifestation of optic neuritis, characterized by inflammatory infiltration and demyelination of the optic nerve, degeneration of retinal ganglion cell bodies had already begun and ultrastructural signs of axon degeneration could be detected. In addition, we observed an early activation of resident microglia in the retina. In the optic nerve, the highest density of activated microglia was found within the optic nerve head. In parallel, localized breakdown in the integrity of the blood–retinal barrier and aberrations in the organization of the blood–brain barrier marker aquaporin-4 in the optic nerves were observed during the preclinical phase, before onset of optic neuritis. From these findings, we conclude that early and subtle inflammatory changes in the retina and/or the optic nerve head reminiscent of those suggested for preclinical MS lesions may initiate the process of neurodegeneration in the retina before major histopathological signs of MS become manifest.
Improving the Efficiency of Relative-Risk Estimation in Case-Cohort Studies

The case-cohort design is a common means of reducing the cost of covariate measurements in large failure-time studies. Under this design, complete covariate data are collected only on the cases (i. e., the subjects whose failure times are uncensored) and on a subcohort randomly selected from the whole cohort. In many applications, certain covariates are readily measured on all cohort members, and surrogate measurements of the expensive covariates also may be available. The existing relative-risk estimators for the case-cohort design disregard the covariate data collected outside the case-cohort sample and thus incur loss of efficiency. To make better use of the available data, we develop a class of weighted estimators with general time-varying weights that are related to a class of estimators proposed by Robins, Rotnitzky, and Zhao. The estimators are shown to be consistent and asymptotically normal under appropriate conditions. We identify the estimator within this class that maximizes efficiency, numerical studies demonstrate that the efficiency gains of the proposed estimator over the existing ones can be substantial in realistic settings. We also study the estimation of the cumulative hazard function. An illustration with data taken from Wilms' tumor studies is provided.
Palmitylation of the influenza virus hemagglutinin (H3) is not essential for virus assembly or infectivity

The C terminus of the influenza virus hemagglutinin (HA) contains three cysteine residues that are highly conserved among HA subtypes, two in the cytoplasmic tail and one in the transmembrane domain. All of these C-terminal cysteine residues are modified by the covalent addition of palmitic acid through a thio-ether linkage. To investigate the role of HA palmitylation in virus assembly, we used reverse genetics technique to introduce substitutions and deletions that affected the three conserved cysteine residues into the H3 subtype HA. The rescued viruses contained the HA of subtype H3 (A/Udorn/72) in a subtype H1 helper virus (A/WSN/33) background. Rescued viruses which do not contain a site for palmitylation (by residue substitution or substitution combined with deletion of the cytoplasmic tail) were obtained. Rescued virions had a normal polypeptide composition. Analysis of the kinetics of HA low-pH-induced fusion of the mutants showed no major change from that of virus with wild-type (wt) HA. The PFU/HA ratio of the rescued viruses grown in eggs ranged from that of virus with wt HA to 16-fold lower levels, whereas the PFU/HA ratio of the rescued viruses grown in MDCK cells varied only 2-fold from that of virus with wt HA. However, except for one rescued mutant virus (CAC), the mutant viruses were attenuated in mice, as indicated by a > or = 400-fold increase in the 50% lethal dose. Interestingly, except for one mutant virus (CAC), all of the rescued mutant viruses were restricted for replication in the upper respiratory tract but much less restricted in the lungs. Thus, the HA cytoplasmic tail may play a very important role in the generation of virus that can replicate in multiple cell types.
Diet-Quality Scores and the Risk of Type 2 Diabetes in Men

OBJECTIVE To 1) compare associations of diet-quality scores, which were inversely associated with cardiovascular disease, with incident type 2 diabetes and 2) test for differences in absolute-risk reduction across various strata. RESEARCH DESIGN AND METHODS Men from the Health Professionals Follow-Up Study, who were initially free of type 2 diabetes, cardiovascular disease, or cancer (n = 41,615), were followed for ≤20 years. The Healthy Eating Index (HEI) 2005, the alternative HEI (aHEI) the Recommended Food Score, the alternative Mediterranean Diet (aMED) Score, and the Dietary Approaches to Stop Hypertension (DASH) Score were calculated from food-frequency questionnaires. Cox proportional hazard models with time-varying covariates were used to assess risk by quintiles and continuous intervals. RESULTS There were 2,795 incident cases of type 2 diabetes. After multivariate adjustment, the aHEI, aMED, and DASH scores were significantly associated with reduced risk. A 1-SD increase was associated with 9–13% reduced risk (P < 0.01), and the DASH score was associated with lower risk independent of other scores. These scores were associated with lower absolute risk among those who were overweight or obese compared with normal weight (P for interaction < 0.01). CONCLUSIONS Several diet-quality scores were associated with a lower risk of type 2 diabetes and reflect a common dietary pattern characterized by high intakes of plant-based foods such as whole grains; moderate alcohol; and low intakes of red and processed meat, sodium, sugar-sweetened beverages, and trans fat. High-quality diets may yield the greatest reduction in diabetes cases when followed by those with a high BMI.
Direct measurement of core temperature in human liver allografts : implications for clinical and research methodology

word count: 145 Text word count: 1494 ∗ To whom correspondence should be addressed at: Carburos Metálicos, S.A. Matapiñonera ,9. 28700 – San Sebastian de los Reyes, Madrid, Spain. Email: gomezsc@carburos.com.
In Vitro Antibacterial Activity of Unconjugated and Conjugated Bile Salts on Staphylococcus aureus

Bile salts are potent antimicrobial agents and are an important component of innate defenses in the intestine, giving protection against invasive organisms. They play an important role in determining microbial ecology of the intestine and alterations in their levels can lead to increased colonization by pathogens. We have previously demonstrated survival of the opportunistic pathogen Staphylococcus aureus in the human colonic model. Thus investigating the interaction between S. aureus and bile salts is an important factor in understanding its ability to colonize in the host intestine. Harnessing bile salts may also give a new avenue to explore in the development of therapeutic strategies to control drug resistant bacteria. Despite this importance, the antibacterial activity of bile salts on S. aureus is poorly understood. In this study, we investigated the antibacterial effects of the major unconjugated and conjugated bile salts on S. aureus. Several concentration-dependent antibacterial mechanisms were found. Unconjugated bile salts at their minimum inhibitory concentration (cholic and deoxycholic acid at 20 and 1 mM, respectively) killed S. aureus, and this was associated with increased membrane disruption and leakage of cellular contents. Unconjugated bile salts (cholic and deoxycholic acid at 8 and 0.4 mM, respectively) and conjugated bile salts (glycocholic and taurocholic acid at 20 mM) at their sub inhibitory concentrations were still able to inhibit growth through disruption of the proton motive force and increased membrane permeability. We also demonstrated that unconjugated bile salts possess more potent antibacterial action on S. aureus than conjugated bile salts.
Recurrent Dropout without Memory Loss

This paper presents a novel approach to recurrent neural network (RNN) regularization. Differently from the widely adopted dropout method, which is applied to forward connections of feedforward architectures or RNNs, we propose to drop neurons directly in recurrent connections in a way that does not cause loss of long-term memory. Our approach is as easy to implement and apply as the regular feed-forward dropout and we demonstrate its effectiveness for the most effective modern recurrent network – Long Short-Term Memory network. Our experiments on three NLP benchmarks show consistent improvements even when combined with conventional feed-forward dropout.
Sequence Learning from Data with Multiple Labels

We present novel algorithms for learning structured predictors from instances with multiple labels in the presence of noise. The proposed algorithms improve performance on two standard NLP tasks when we have a small amount of training data (low quantity) and when the labels are noisy (low quality). In these settings, the methods improve performance over using a single label, in some cases exceeding performance using gold labels. Our methods could be used in a semi-supervised setting, where a limited amount of labeled data could be combined with a rule based automatic labeling of unlabeled data with multiple possible labels.
Dystroglycan in the Cerebellum is a Laminin α2‐chain Binding Protein at the Glial‐Vascular Interface and is Expressed in Purkinje cells

Dystroglycan is a core component of the dystrophin receptor complex in skeletal muscle which links the extracellular matrix to the muscle cytoskeleton. Dystrophin, dystrophin‐related protein (DRP, utrophin) and dystroglycan are present not only in muscles but also in the brain. Dystrophin is expressed in certain neuronal populations while DRP is associated with perivascular astrocytes. To gain insights into the function and molecular interactions of dystroglycan in the brain, we examined the localization of α‐and β‐dystroglycan at the cellular and subcellular levels in the rat cerebellum. In blood vessels, we find a‐dystroglycan associated with the laminin a2‐chain‐rich parenchymal vascular basement membrane and β‐dystroglycan associated with the endfeet of perivascular astrocytes. We also show that a‐dystroglycan purified from the brain binds a2‐chain‐containing laminin‐2. These observations suggest a dystroglycan‐mediated linkage between DRP in perivascular astrocytic endfeet and laminin‐2 in the parenchymal basement membrane similar to that described in skeletal muscle. This linkage of the astrocytic endfeet to the vascular basement membrane is likely to be important for blood vessel formation and stabilization and for maintaining the integrity of the blood‐brain barrier. In addition to blood vessel labelling, we show that β‐dystroglycan in the rat cerebellum is associated with the surface of Purkinje cell bodies, dendrites and dendritic spines. Dystrophin has previously been localized to the inner surface of the plasma membrane of Purkinje cells and is enriched at postsynaptic sites. Thus, the present results also support the hypothesis that dystrophin interacts with dystroglycan in cerebellar Purkinje neurons.
Benefits of a Ball and Chain: Simple Environmental Enrichments Improve Welfare and Reproductive Success in Farmed American Mink (Neovison vison)

Can simple enrichments enhance caged mink welfare? Pilot data from 756 sub-adults spanning three colour-types (strains) identified potentially practical enrichments, and suggested beneficial effects on temperament and fur-chewing. Our main experiment started with 2032 Black mink on three farms: from each of 508 families, one juvenile male-female pair was enriched (E) with two balls and a hanging plastic chain or length of hose, while a second pair was left as a non-enriched (NE) control. At 8 months, more than half the subjects were killed for pelts, and 302 new females were recruited (half enriched: ‘late E’). Several signs of improved welfare or productivity emerged. Access to enrichment increased play in juveniles. E mink were calmer (less aggressive in temperament tests; quieter when handled; less fearful, if male), and less likely to fur-chew, although other stereotypic behaviours were not reduced. On one farm, E females had lower cortisol (inferred from faecal metabolites). E males tended to copulate for longer. E females also weaned more offspring: about 10% more juveniles per E female, primarily caused by reduced rates of barrenness (‘late E’ females also giving birth to bigger litters on one farm), effects that our data cautiously suggest were partly mediated by reduced inactivity and changes in temperament. Pelt quality seemed unaffected, but E animals had cleaner cages. In a subsidiary side-study using 368 mink of a second colour-type (‘Demis’), similar temperament effects emerged, and while E did not reduce fur-chewing or improve reproductive success in this colour-type, E animals were judged to have better pelts. Overall, simple enrichments were thus beneficial. These findings should encourage welfare improvements on fur farms (which house 60-70 million mink p.a.) and in breeding centres where endangered mustelids (e.g. black-footed ferrets) often reproduce poorly. They should also stimulate future research into more effective practical enrichments.
Oculomotor Guidance and Capture by Irrelevant Faces

Even though it is generally agreed that face stimuli constitute a special class of stimuli, which are treated preferentially by our visual system, it remains unclear whether faces can capture attention in a stimulus-driven manner. Moreover, there is a long-standing debate regarding the mechanism underlying the preferential bias of selecting faces. Some claim that faces constitute a set of special low-level features to which our visual system is tuned; others claim that the visual system is capable of extracting the meaning of faces very rapidly, driving attentional selection. Those debates continue because many studies contain methodological peculiarities and manipulations that prevent a definitive conclusion. Here, we present a new visual search task in which observers had to make a saccade to a uniquely colored circle while completely irrelevant objects were also present in the visual field. The results indicate that faces capture and guide the eyes more than other animated objects and that our visual system is not only tuned to the low-level features that make up a face but also to its meaning.
Growth of Campylobacter jejuni on nitrate and nitrite: electron transport to NapA and NrfA via NrfH and distinct roles for NrfA and the globin Cgb in protection against nitrosative stress

Pathways of electron transport to periplasmic nitrate (NapA) and nitrite (NrfA) reductases have been investigated in Campylobacter jejuni, a microaerophilic food‐borne pathogen. The nap operon is unusual in lacking napC (encoding a tetra‐haem c‐type cytochrome) and napF, but contains a novel gene of unknown function, napL. The iron‐sulphur protein NapG has a major role in electron transfer to the NapAB complex, but we show that slow nitrate‐dependent growth of a napG mutant can be sustained by electron transfer from NrfH, the electron donor to the nitrite reductase NrfA. A napL mutant possessed ∼50% lower NapA activity than the wild type but showed normal growth with nitrate as the electron acceptor. NrfA was constitutive and was shown to play a role in protection against nitrosative stress in addition to the previously identified NO‐inducible single domain globin, Cgb. However, nitrite also induced cgb expression in an NssR‐dependent manner, suggesting that growth of C. jejuni with nitrite causes nitrosative stress. This was confirmed by lack of growth of cgb and nssR mutants, and slow growth of the nrfA mutant, in media containing nitrite. Thus, NrfA and Cgb together provide C. jejuni with constitutive and inducible components of a robust defence against nitrosative stress.
Pulmonary haemodynamics in patients with OSAS or an overlap syndrome.

BACKGROUND Alveolar hypoxia is the most important mechanism leading to pulmonary arterial vasoconstriction, remodelling and pulmonary hypertension. Patients with Obstructive Sleep Apnoea Syndrome (OSAS) experience multiple short periods of alveolar hypoxia during apnoeic episodes. However, the question as to whether these hypoxic episodes are responsible for the development of permanent pulmonary hypertension is still debatable. We aimed to investigate the relationship between the episodes of nocturnal desaturation and pulmonary haemodynamics in two distinct group patients: with pure OSAS or an overlap syndrome. METHODS We studied 67 patients with severe OSAS (means: age 45+/-8 years, AHI 62+/-22, FEV1 3.6+/-0.8 L = 97+/-16% of predicted PaO2 72+/-10 mmHg, PaCO2 40+/-4 mmHg) and 17 patients with an overlap syndrome (OS), means: age 51+/-5 years, AHI 64+/-19, FEV1 1.5+/-0.7 = 43+/-16% of predicted PaO2 57+/-9 mmHg). All subjects underwent pulmonary artery catheterisation with pressure and flow recordings and an overnight full sleep study. RESULTS On average patients with OSAS had nocturnal desaturation (mean overnight SaO2 = 87+/-5%) and normal PPA (15.8+/-4.6 mmHg). Only 11 out of 67 subjects (16%) presented with pulmonary hypertension. Patients with OS had nocturnal desaturation (mean overnight SaO2 = 80.2+/-8.5%) and mild pulmonary hypertension (PPA 24.2+/-7.4 mmHg). Only three out of 17 patients had normal pulmonary arterial pressure. CONCLUSIONS In patients with severe OSAS, pulmonary hypertension is rare (16%) and is related best to the severity of the disease and to obesity. In OS patients diurnal pulmonary hypertension is frequent but does not correlate with the severity of nocturnal desaturation.
Insecticide Residues on Poultry Manures: Field Efficacy Test on Selected Insecticides in Managing Musca Domestica Population

In this study, bifenthrin (Maxxthor SC, Ensystex Australasia Pty Ltd), imidacloprid (Prothor SC, Ensystex Australasia Pty Ltd) and fipronil (Regent®50SC, Bayer) were applied on the natural infest manures according to the manufacturer rate during a broiler breeding cycle. Solvent direct-immersion extraction (SDIE) was used in detecting the target compound and later, quantification of the insecticide residues in field condition was investigated. The samples were prior cleaned up by solid-phase extraction (SPE) and analysed by Ultra-Performance Liquid Chromatography (UPLC) – photodiode array (PDA) system. In the field trial, three insecticides were showed accumulation during the broiler breeding period and it is suggested that they acted as adulticides when applied on the poultry manures, this is supported by the significant correlation between the increment of insecticide residues to the reduction percentage of adult flies (<0.05). Fipronil showed significantly greater reduction on the adult fly compared to the other insecticides, in which the reduction rate compared to control population at the end of the broiler breeding period; fipronil, imidaclopril and bifenthrin reduced 51.51%, 28.30% and 30.84% of adult flies, respectively.