Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in respiratory sensations induced by lobeline after human bilateral lung transplantation

1 The sensations evoked by the injection of lobeline into the right antecubital vein were studied in 8 subjects after bilateral lung transplantation and 10 control subjects. In control subjects, two distinct sensations were experienced. There was an early noxious sensation (onset ≈10 s) followed by a late sensation of breathlessness (onset ≈26 s) associated with involuntary hyperventilation. The early sensation was accompanied by respiratory and cardiovascular changes. 2 In contrast to control subjects, the early respiratory events and the noxious sensations evoked by injections of lobeline (18‐60 μg kg−1) did not occur in subjects with recent bilateral lung transplantation. This suggests that the early respiratory sensations are mediated by the discharge of receptors in the lungs. 3 The late hyperventilation and the accompanying sensation of breathlessness occurred in both transplant and control subjects and are therefore likely to be mediated by receptors elsewhere in the body, presumably systemic arterial chemoreceptors stimulated by lobeline. 4 In control subjects, but not transplant subjects, there was a consistent decrease in mean arterial pressure associated with the lobeline injection. This suggests that pulmonary afferents mediate the hypotension. 5 For transplant subjects studied more than a year after transplantation, there was some evidence that the noxious respiratory sensations evoked by lobeline had returned. This suggests that some functional reinnervation of pulmonary afferents may occur.
TLR3-Stimulated Dendritic Cells Up-regulate B7-H1 Expression and Influence the Magnitude of CD8 T Cell Responses to Tumor Vaccination1

Agonists of TLR have been explored as vaccine adjuvants for tumor immunotherapy. However, their immunological consequences are not fully understood. Although TLR signaling increases the functional potential of dendritic cells (DCs) for priming T cells, coinduction of potentially negative immunoregulatory capacities may impair effector T cell generation. We examined the expression and function of B7 family costimulatory molecules on DCs after activation with the TLR3 agonist, polyinosinic:polycytidylic acid. We demonstrated that polyinosinic:polycytidylic acid consistently up-regulated both B7-2 and B7-H1 molecules on resident, migratory DCs from spleen and lymph nodes. Depletion or blockade of B7-H1 on activated DCs increased the magnitude of effector CD8 T cell expansion. DC-based or protein-based tumor vaccines, in combination with B7-H1 blockade, induced strong effector CD8 T cell responses, resulting in protective immunity against newly established tumors. Our studies suggest that TLR3 signaling has the potential to up-regulate both positive and negative coregulatory molecules on APCs. Selective blockade of negative regulatory molecules in combination with TLR3 agonist may be an effective strategy for increasing the efficacy of tumor vaccines.
Dopamine release is impaired in a mouse model of DYT1 dystonia

Early onset torsion dystonia, the most common form of hereditary primary dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein torsinA. This form of dystonia is referred to as DYT1. We have used a transgenic mouse model of DYT1 dystonia [human mutant‐type (hMT)1 mice] to examine the effect of the mutant human torsinA protein on striatal dopaminergic function. Analysis of striatal tissue dopamine (DA) and metabolites using HPLC revealed no difference between hMT1 mice and their non‐transgenic littermates. Pre‐synaptic DA transporters were studied using in vitro autoradiography with [3H]mazindol, a ligand for the membrane DA transporter, and [3H]dihydrotetrabenazine, a ligand for the vesicular monoamine transporter. No difference in the density of striatal DA transporter or vesicular monoamine transporter binding sites was observed. Post‐synaptic receptors were studied using [3H]SCH‐23390, a ligand for D1 class receptors, [3H]YM‐09151‐2 and a ligand for D2 class receptors. There were again no differences in the density of striatal binding sites for these ligands. Using in vivo microdialysis in awake animals, we studied basal as well as amphetamine‐stimulated striatal extracellular DA levels. Basal extracellular DA levels were similar, but the response to amphetamine was markedly attenuated in the hMT1 mice compared with their non‐transgenic littermates (253 ± 71% vs. 561 ± 132%, p < 0.05, two‐way anova). These observations suggest that the mutation in the torsinA protein responsible for DYT1 dystonia may interfere with transport or release of DA, but does not alter pre‐synaptic transporters or post‐synaptic DA receptors. The defect in DA release as observed may contribute to the abnormalities in motor learning as previously documented in this transgenic mouse model, and may contribute to the clinical symptoms of the human disorder.
Cytogenomic assessment of the diagnosis of 93 patients with developmental delay and multiple congenital abnormalities: The Brazilian experience

OBJECTIVE: The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients. METHODS: We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays. RESULTS: Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected ∼70.6% of pathogenic changes. CONCLUSION: The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis.
Micronutrient Intake and the Presence of the Metabolic Syndrome

Background: Dietary micronutrients have been proposed to protect against oxidative damage and related clinical complications. Aims: We aimed to compare the micronutrient intake between individuals with and without metabolic syndrome (MS). Materials and Methods: This cross-sectional study included 3800 men and women who were aged between 35 and 65 years. The diagnosis of the MS was based on International Diabetes Federation criteria. Dietary intake of participants was assessed using a questionnaire for 24 h dietary recall. Student's t-test and Mann–Whitney U-tests were used for comparing the micronutrient intake of subjects with or without the MS and the odds ratio for the presence of the MS was calculated for each micronutrient by control for total energy intake adjusted by the residue method. Results: The mean age of MS subjects and the control group was 48.8 ± 7.9 years and 47.6 ± 7.6 years, respectively. Energy-adjusted intake of vitamin E (P < 0.05), B2 (P < 0.01), and B12 (P < 0.05) was higher in normal women compared with women with MS. Energy-adjusted intake of vitamin B1 was significantly higher in women with MS. After logistic regression analysis, no significant association between micronutrient intake and MS was shown. Conclusion: We found no significant association between micronutrient intake and MS.
The unexpected and large enhancement of the dipole moment in the 3,4-bis(dimethylamino)-3-cyclobutene-1,2-dione (DMACB) molecule upon crystallization: a new role of the intermolecular CH...O interactions.

The molecular dipole moment of the 3,4-bis(dimethylamino)-3-cyclobutene-1,2-dione (DMACB) molecule and its enhancement in the crystal was evaluated by periodic RHF ab initio computations. A discrete boundary partitioning of the electronic density that allows an unambiguous partitioning of the molecular space in the condensed phase was adopted. The resulting molecular dipole in the crystal compares favorably with the experimental value obtained by a multipolar analysis of single-crystal X-ray diffraction data recorded at 20 K, using a fuzzy boundary partitioning of the derived pseudoatom densities. We show that a large and highly significant molecular dipole enhancement may occur upon crystallization, despite the lack of a strongly hydrogen bonded environment in the crystal. The 23 unique C-H.O interactions which are formed upon packing of the DMACB molecule induce an increase in the molecular dipole (over 75%) that is comparable to or greater than that found in systems which are characterized by the stronger O-H.O and N-H.O hydrogen bonds. The DMACB molecule constitutes an excellent system for the study of C-H.O interactions in the condensed phase, since no other kind of competing hydrogen bonds is present in its crystal. A simple and qualitative model for the matrix contribution to the DMACB molecular dipole enhancement in the crystal is proposed. The formation of several weak C-H.O bonds is found to yield a small (about 0.2 e) net flux of electronic charge flowing from the hydrogens of the methyl groups to the carbonyl oxygen atoms. Despite the limited increase of the intramolecular charge transfer upon crystallization, a large molecular dipole enhancement occurs because the centroids of the positive and negative induced charges are quite far apart. This work highlights a new and important role of the C-H.O bond, besides those already known in the literature.
Molecular Aspects of Microcystin-induced Hepatotoxicity and Hepatocarcinogenesis

It is known that microcystin (MC) is a cyanotoxin that is a potent environmental inhibitor of eucariotic protein serine/threonine phosphatase 1 and 2A, both in vitro and in vivo. Consequently, these cyanobacterial toxins (MC–IARC group 2B carcinogen, MC extracts–group 3) are potent tumor promoters and there is an indication that they may also act as tumor initiators. The ability of microcystin-LR (MC-LR) to act as a tumor initiator is based on fact that it can induce DNA damage either by direct interaction with DNA or by indirect mechanisms through formation of reactive oxygen species (ROS). Both acute and chronic exposures, to either low or high doses of MC-LR, can activate apoptotic pathways. Chronic exposure to low concentrations of MC-LR contributes to increased risk for cancer development. Epidemiological studies, in certain areas of China, have suggested that MC is one of the risk factors for the high incidence of primary liver cancer (PLC). Recently, we have reported a correlation between PLC and cyanobacterial “blooms” in reservoirs used as a source for drinking water supply in central Serbia. It appears that the combination of acute and chronic exposures to both high and low doses of MC can lead to PLC initiation and promotion. Based on this, we propose that the requirement for the co-factors such as aflatoxin B1 and other mycotoxins, HBV, HCV, alcohol, etc. is not needed for initiation and promotion of PLC by MC-LR as was suggested earlier. The possible mechanisms of the genotoxicity of MC and its role as a hepatocarcinogen are outlined in this review. Furthermore, we show that the exposure of hepatocytes to MC can lead either to malignant proliferation or apoptosis.
Differentiation vs. price in consumer choice

Internet shopbots allow consumers to almost instantly compare prices and other characteristics from dozens of sellers via a single website. We estimate the magnitude of consumer search costs and benefits using data from a major shopbot for books. For the median consumer, the estimated benefit from simply scrolling down to search lower screens is $6.55. This amounts to about 60% of the observed price dispersion and suggests that consumers face significant search costs, even in this "nearly-perfect" market. Price elasticities are relatively high compared to offline markets (− 7t o−10 in our base model). Furthermore, contrary to the common assumption, search intensity is not correlated with greater price sensitivity. Instead, consumers who search multiple screens put relatively more weight on non-price factors like brand.
Disruption of lipid order by short-chain ceramides correlates with inhibition of phospholipase D and downstream signaling by FcϵRI

Specialized plasma membrane domains known as lipid rafts participate in signal transduction and other cellular processes, and their liquid-ordered properties appear to be important for their function. We investigated the possibility of using amphiphiles to disrupt lipid rafts and thereby inhibit IgE-FcϵRI signaling. We find that short-chain ceramides – C2-ceramide and C6-ceramide – decrease plasma membrane lipid order and reduce the extent of fluorescence resonance energy transfer between lipid-raft-associated molecules on intact cells; by contrast, biologically inactive C2-dihydroceramide does neither. Structural perturbations by these ceramides parallel their inhibitory effects on antigen-stimulated Ca2+ mobilization in RBL mast cells in the presence and absence of extracellular Ca2+. Similar inhibition of Ca2+ mobilization is caused by n-butanol, which prevents phosphatidic acid production by phospholipase D, but not by t-butanol, which does not prevent phosphatidic acid production. These results and previously reported effects of short-chain ceramides on phospholipase D activity prompted us to compare the effects of C2-ceramide, C2-dihydroceramide and C16-ceramide on phospholipase D1 and phospholipase D2 activities in vitro. We find that the effects of these ceramides on phospholipase D1 activity strongly correlate with their effects on antigen-stimulated Ca2+ mobilization and with their disruption of lipid order. Our results indicate that phospholipase D activity is upstream of antigen-stimulated Ca2+ mobilization in these cells, and they demonstrate that ceramides can serve as useful probes for investigating roles of plasma membrane structure and phospholipase D activity in cellular signaling.
Analysis of the DECREASED APICAL DOMINANCE Genes of Petunia in the Control of Axillary Branching1[C][OA]

Control of branch development is a major determinant of architecture in plants. Branching in petunia (Petunia hybrida) is controlled by the DECREASED APICAL DOMINANCE (DAD) genes. Gene functions were investigated by plant grafting, morphology studies, double-mutant characterization, and gene expression analysis. Both dad1-1 and dad3 increased branching mutants can be reverted to a near-wild-type phenotype by grafting to a wild-type or a dad2 mutant root stock, indicating that both genes affect the production of a graft-transmissible substance that controls branching. Expression of the DAD1 gene in the stems of grafted plants, detected by quantitative reverse transcription-polymerase chain reaction correlates with the branching phenotype of the plants. The dad2-1 mutant cannot be reverted by grafting, indicating that this gene acts predominantly in the shoot of the plant. Double-mutant analysis indicates that the DAD2 gene acts in the same pathway as the DAD1 and DAD3 genes because the dad1-1dad2-1 and dad2-1dad3 double mutants are indistinguishable from the dad2-1 mutant. However, the dad1-1dad3 double mutant has an additive phenotype, with decreased height of the plants, delayed flowering, and reduced germination rates compared to the single mutants. This result, together with the observation that the dad1-1 and dad3 mutants cannot be reverted by grafting to each other, suggests that the DAD1 and DAD3 genes act in the same pathway, but not in a simple stepwise fashion.
MicroRNA regulation of the paired-box transcription factor Pax3 confers robustness to developmental timing of myogenesis

Commitment of progenitors in the dermomyotome to myoblast fate is the first step in establishing the body musculature. Pax3 is a crucial transcription factor, important for skeletal muscle development and expressed in myogenic progenitors in the dermomyotome of developing somites and in migratory muscle progenitors that populate the limb buds. Down-regulation of Pax3 is essential to ignite the myogenic program, including up-regulation of myogenic regulators, Myf-5 and MyoD. MicroRNAs (miRNAs) confer robustness to developmental timing by posttranscriptional repression of genetic programs that are related to previous developmental stages or to alternative cell fates. Here we demonstrate that the muscle-specific miRNAs miR-1 and miR-206 directly target Pax3. Antagomir-mediated inhibition of miR-1/miR-206 led to delayed myogenic differentiation in developing somites, as shown by transient loss of myogenin expression. This correlated with increased Pax3 and was phenocopied using Pax3-specific target protectors. Loss of myogenin after antagomir injection was rescued by Pax3 knockdown using a splice morpholino, suggesting that miR-1/miR-206 control somite myogenesis primarily through interactions with Pax3. Our studies reveal an important role for miR-1/miR-206 in providing precision to the timing of somite myogenesis. We propose that posttranscriptional control of Pax3 downstream of miR-1/miR-206 is required to stabilize myoblast commitment and subsequent differentiation. Given that mutually exclusive expression of miRNAs and their targets is a prevailing theme in development, our findings suggest that miRNA may provide a general mechanism for the unequivocal commitment underlying stem cell differentiation.
Ad-hoc Runtime Object Structure Visualizations with MetaLinks

This paper describes an original method and a tool for an a posteriori analysis of a running object software system, specifically system's runtime structural properties. Highly context-dependent systems pose a challenge of understanding their runtime behaviour. The typical approach is to let the system run and manually observe its runtime properties, which is cognitively demanding and error-prone. Smalltalk, and Pharo in particular, focuses on providing live introspection and immediate feedback during the development. In our method, we take the advantage of these possibilities and combine them with the (relatively new) concept of metalinks as a way to hook into existing code without modifying it, and to set specific attributes to be observed. The result is an analysis tool focused on visualization of ad-hoc runtime structures -- that is, providing an analyst with a live view of the stepwise construction and runtime changes of a system based on a UML instance visualization. We demonstrate the tool on analyzing the construction loop of Pharo's Spec UI framework.
Will European agricultural policy for school fruit and vegetables improve public health? A review of school fruit and vegetable programmes.

BACKGROUND For the first time, public health, particularly obesity, is being seen as a driver of EU agricultural policy. In 2007, European Ministers of Agriculture were asked to back new proposals for school fruit and vegetable programmes as part of agricultural reforms. In 2008, the European Commission conducted an impact assessment to assess the potential impact of this new proposal on health, agricultural markets, social equality and regional cohesion. METHODS A systematic review of the effectiveness of interventions to promote fruit and/or vegetable consumption in children in schools, to inform the EC policy development process. RESULTS School schemes are effective at increasing both intake and knowledge. Of the 30 studies included, 70% increased fruits and vegetables (FV) intake, with none decreasing intake. Twenty-three studies had follow-up periods >1 year and provide some evidence that FV schemes can have long-term impacts on consumption. Only one study led to both increased fruit and vegetable intake and reduction in weight. One study showed that school fruit and vegetable schemes can also help to reduce inequalities in diet. Effective school programmes have used a range of approaches and been organized in ways which vary nationally depending on differences in food supply chain and education systems. CONCLUSIONS EU agriculture policy for school fruits and vegetables schemes should be an effective approach with both public health and agricultural benefits. Aiming to increase FV intake amongst a new generation of consumers, it will support a range of EU policies including obesity and health inequalities.
Endemic Variation of H9N2 Avian Influenza Virus in China

SUMMARY Forty-two H9N2 subtype AIV strains were isolated from vaccinated commercial chickens in China from 2012 to 2015. Their HA genes had nucleotide sequence homology from 86.7% to 99.7%, and similarity to the classic vaccine strain was 88.6%–92.6%. A comparison was carried out with published HA genes (410 H9 strains) and whole genomes (306 strains) isolated in China during 2012–2015. Interestingly, 99.1% (448/452) of Chinese H9N2 AIV belonged to lineage h9.4. 2, and 98.5% (445/452) of the viruses belonged to h9.4. 2.5. Meanwhile, 99.6% (443/445) of lineage 9.4. 2.5 viruses had PSRSSR↓GLF instead of PARSSR↓GLF motifs in the HA cleavage sites; 98.2% (444/452) of HA genes showed human receptor binding associated mutation Q226L. A total of 96.8% (337/348) of the viruses had three amino-acid deletions at 63–65 in the NA stalk, associated with enhanced virulence in chickens and mice; 97.1% (338/348) of M2 proteins had the S31N mutation associated with adamantane resistance in humans. Two H9 viruses isolated in this study were highly homologous to the human-origin H9N2 virus reported in 2013. The isolates were divided into four different genotypes (U, S, V, and W). Genotype S was the major one, accounting for 94.8% (330/348). Genotypes V and W were new reassortment genotypes, with genotype W recombined with the PB2 gene originating from the new wild waterfowl-like lineage. According to the cross-HI antibody titer data, HA gene evolution, and isolation history, the isolates were divided into A, B, and C antigenic groups successively. All the antigenic group viruses were found to circulate throughout China. This study emphasizes the importance of updated vaccine and strengthened veterinary biosecurity on poultry farms and trade markets.