Miracle-dz/UniFAR-FTUs huggingface dataset:
Nutritional habits of middle-aged schoolchildren from Kaunas town and Raseiniai district.

OBJECTIVE To evaluate nutritional habits of middle-aged schoolchildren living in a town and district of Lithuania. MATERIAL AND METHODS The 8th-9th-grade schoolchildren were questioned by an anonymous questionnaire. A total of 329 students, 169 from Kaunas and 160 from Raseiniai district, participated in the study. RESULTS Only half of students reported that they had breakfast (61.3% of schoolboys and 47.6% of schoolgirls). More students from the district had dinner in the school canteen as compared to Kaunas students. Only 14.0% of schoolchildren followed nutrition regimen (14.8% of students from Kaunas and 13.1% of students from Raseiniai always had their meal at the same time). Every second schoolboy and schoolgirl consumed vegetables and fruits every day. Whole grain bread was consumed every day similarly frequently by students from Kaunas and Raseiniai, 25.4% and 18.8%, respectively; the students from Kaunas consumed skim milk more frequently, 26.0% and 11.9%, respectively (P<0.05). Confectionery was consumed more frequently by schoolchildren from Kaunas as compared to schoolchildren from Raseiniai district (63.9% vs. 55.0%); however, it was consumed more frequently by boys than girls. Less than one-fourth of Kaunas students (20.7%) consumed potato chips every day, whereas the percentage of the students from Raseiniai district was only 10.0% (P<0.05). Pizzas, kebabs, and hamburgers were consumed more frequently by schoolboys than schoolgirls. Knowledge of healthy nutrition was obtained mainly from media by 48.6% of students; every eighth student got this information from parents, every tenth from physicians, and 7.0% from teachers. CONCLUSIONS Middle-aged students from both Kaunas town and Raseiniai district did not follow nutrition regimen; half of them did not have their breakfast before going to school. Fruits and vegetables as recommended foods were consumed by half of the participants; every fourth student consumed skim milk, and every fifth student consumed whole grain bread. The students more frequently consumed such foods as confectionery and smoked meat, which are not recommended (every second student); every fourth had an intake of carbonated drinks (the students from Kaunas more frequently) and potato chips (the students from Kaunas more frequently), and every tenth consumed pizzas and fried potatoes. More than half of students obtained knowledge of healthy nutrition from media, and every tenth--from the physicians.
Differential Localization of the Streptococcal Accessory Sec Components and Implications for Substrate Export

ABSTRACT The accessory Sec system of Streptococcus gordonii is comprised of SecY2, SecA2, and five proteins (Asp1 through -5) that are required for the export of a serine-rich glycoprotein, GspB. We have previously shown that a number of the Asps interact with GspB, SecA2, or each other. To further define the roles of these Asps in export, we examined their subcellular localization in S. gordonii and in Escherichia coli expressing the streptococcal accessory Sec system. In particular, we assessed how the locations of these accessory Sec proteins were altered by the presence of other components. Using fluorescence microscopy, we found in E. coli that SecA2 localized within multiple foci at the cell membrane, regardless of whether other accessory Sec proteins were expressed. Asp2 alone localized to the cell poles but formed a similar punctate pattern at the membrane when SecA2 was present. Asp1 and Asp3 localized diffusely in the cytosol when expressed alone or with SecA2. However, these proteins redistributed to the membrane in a punctate arrangement when all of the accessory Sec components were present. Cell fractionation studies with S. gordonii further corroborated these microscopy results. Collectively, these findings indicate that Asp1 to -3 are not integral membrane proteins that form structural parts of the translocation channel. Instead, SecA2 serves as a docking site for Asp2, which in turn attracts a complex of Asp1 and Asp3 to the membrane. These protein interactions may be important for the trafficking of GspB to the cell membrane and its subsequent translocation.
Structure-Function Studies of Epoxide Hydrolases

Epoxides are three-membered cyclic ethers formed in cells via several metabolic pathways. Epoxide hydrolases (EHs) are enzymes that hydrolyse epoxides to the corresponding diols. The main goal of this thesis was to investigate the structures of EHs from the alpha/beta-hydrolase family. The first part concerns the structural and functional analysis of a protein-water channel found in EHs in many plants. Thermostability studies, sequence analysis and determination of the x-ray structure of a mutated EH enzyme from Solanum tuberosum led to the conclusions that the water channel in plants participates in stabilization of the protein structure and furthermore, it forms an efficient system to enable transfer of protons that are required for enzymatic catalysis. The second part describes how computational methods together with structural and kinetic information identified factors that are responsible for the enhanced enantioselectivity of an improved variant of EH from Aspergillus niger obtained during a directed evolution process. The x-ray structure of the mutant showed that dramatic changes in the active site explain why the preferred (S)-substrate binds more easily in the active site than the disfavored (R)-enantiomer. The study underscores the importance of obtaining structural data when attempting to understand the results of directed evolution. The last part presents the structures of two novel microbial EHs that have been shown to produce chemically valuable 1,2-diols and exhibit high enantioselectivity. Their similarity to the mammalian microsomal EH, a key enzyme in detoxification, provided new information about its possible structure. The improved sequence alignment based on the structural work gives new insights on the connections between sequences/structures and the broad scope of selectivities among EHs.
Early expression of IFN-alpha/beta and iNOS in the brains of Venezuelan equine encephalitis virus-infected mice.

To investigate the roles of type I interferon (IFN-alpha/beta) and other mediators of innate immune responses (e.g., inducible nitric oxide synthase [iNOS]) in early dissemination of Venezuelan equine encephalitis virus (VEE) infection, we used mice with targeted deletions in either their IFN-alpha/beta-receptor (IFNAR-1-/-) or interferon regulatory factor 2 (IRF-2-/-) genes. Following footpad infection, both IFNAR-1-/- and IRF-2-/- mice were more susceptible than control mice to VEE. The IFNAR-1-/- mice also exhibit accelerated VEE dissemination to serum, spleen, and brain, and compared with control mice, they evidenced faster kinetics in the upregulation of proinflammatory genes. In contrast, in IRF-2-/- mice, iNOS gene induction was completely absent following peripheral virulent VEE infection. In evaluating the role of cells involved in iNOS production, primary microglial cell cultures were found to be highly permissive to VEE infection. Moreover, VEE infection increased levels of nitric oxide (NO) in resting microglial cultures but decreased NO production in IFN-gamma-stimulated microglia. Thus, these findings suggest that reactive nitrogen species play an important contributory role in VEE dissemination and survival of the host. Our results further suggest the necessity for a carefully balanced host response that follows a middle course between immunopathology and insufficient inflammatory response to VEE infection.
Different misfolding mechanisms converge on common conformational changes

Prion diseases are caused by misfolding and aggregation of the prion protein (PrP). Pathogenic mutations such as Y218N and E196K are known to cause Gerstmann-Sträussler-Scheinker syndrome and Creutzfeldt-Jakob disease, respectively. Here we describe molecular dynamics simulations of these mutant proteins to better characterize the detailed conformational effects of these sequence substitutions. Our results indicate that the mutations disrupt the wild-type native PrPC structure and cause misfolding. Y218N reduced hydrophobic packing around the X-loop (residues 165–171), and E196K abolished an important wild-type salt bridge. While differences in the mutation site led PrP mutants to misfold along different pathways, we observed multiple traits of misfolding that were common to both mutants. Common traits of misfolding included: 1) detachment of the short helix (HA) from the PrP core; 2) exposure of side chain F198; and 3) formation of a nonnative strand at the N-terminus. The effect of the E196K mutation directly abolished the wild-type salt bridge E196-R156, which further destabilized the F198 hydrophobic pocket and HA. The Y218N mutation propagated its effect by increasing the HB-HC interhelical angle, which in turn disrupted the packing around F198. Furthermore, a nonnative contact formed between E221 and S132 on the S1-HA loop, which offered a direct mechanism for disrupting the hydrophobic packing between the S1-HA loop and HC. While there were common misfolding features shared between Y218N and E196K, the differences in the orientation of HB and HC and the X-loop conformation might provide a structural basis for identifying different prion strains.
Golimumab in refractory uveitis associated to juvenile idiopathic arthritis: multicentre study of 7 cases and literature review.

OBJECTIVES To assess the efficacy of golimumab (GLM), a fully humanised anti-TNF-α monoclonal antibody, in refractory juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS This was a multicentre study of JIA-associated uveitis refractory to standard synthetic immunosuppressive drugs and in most cases to other anti-TNF-α agents. Results were expressed as mean±standard deviation or as median (range or interquartile range). The Wilcoxon signed-rank test was used to compare continuous variables. A literature review of the efficacy of GLM in uveitis related to JIA was also conducted. RESULTS We studied 7 patients (5 females; mean age 21.7±7.5 years; 13 affected eyes). Uveitis was bilateral in 6. Cystoid macular oedema (CME) occurred in 3 patients (5 eyes). Besides corticosteroids and synthetic immunosuppressive drugs, patients had received before GLM a median of 2 biologic agents (range 0-3) including adalimumab (n=6), etanercept (n=2), infliximab (n=3) and abatacept (n=2). GLM dose was 50 mg/sc every 4 weeks. After 6 months of therapy the number of anterior chamber cells decreased from 1 [0.25-1.5] to 0 [0-0.5] (p=0.02) and optical coherence tomography (in patients with CME) from 313.6±77.05 to 261.4±75.1 μm (p=0.03). The best-corrected visual acuity increased from 0.5 to 0.62 (p=0.018). Complete remission of uveitis was achieved in 4 of 7 patients after 16.8±11.4 months of follow-up. However, 2 of the seven patients had to be switched to tocilizumab due to inefficacy. Local erythema at the injection site was observed in 2. CONCLUSIONS GLM may be considered in the management of refractory JIA-related uveitis.
Macrophage Apolipoprotein E Reduces Atherosclerosis and Prevents Premature Death in Apolipoprotein E and Scavenger Receptor–Class BI Double-Knockout Mice

Objective—Mice null for both apolipoprotein (apo)E and scavenger receptor (SR)-BI (DKO) develop severe hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarction, and premature death. The current study examines the ability of macrophage apoE to improve the dyslipidemia, reduce atherosclerosis, and rescue the lethal phenotype of DKO mice. Methods and Results—Initially, bone marrow transplantation (BMT) was unsuccessful, because the DKO mice died from a rapidly fatal anemia 3 to 5 days after lethal irradiation. Therefore, probucol was used to rescue the DKO mice during BMT and was discontinued 2-weeks after BMT, allowing successful reconstitution with donor marrow. Twelve male apoE−/−SR-BI−/− mice fed 0.5% probucol in a chow diet were lethally irradiated and transplanted with either wild-type (WT) or DKO bone marrow. Two-weeks after BMT, apoE was detected in serum in WT→DKO mice, and mean serum cholesterol levels were reduced by 70% versus DKO→DKO mice. Lipoprotein profiles and HDL subpopulations in WT→DKO mice were similar to apoE+/+SR-BI−/−→DKO mice and resembled those of SR-BI−/− mice. In WT→DKO mice, aortic atherosclerosis was reduced by 88% to 90% versus DKO→DKO mice. Furthermore, the DKO→DKO mice died ≈8 weeks after BMT, whereas WT→DKO mice exhibited a life span >40 weeks after BMT. Conclusions—Macrophage apoE is able to rescue the lethal phenotype of apoE−/−SR-BI−/− mice by improving the dyslipidemia and dramatically reducing atherosclerotic lesion development.
Myogenic cell cycle duration in Harpagifer species with sub-Antarctic and Antarctic distributions: evidence for cold compensation

SUMMARY In teleosts, the proliferation of myogenic progenitor cells is required for muscle growth and nuclear turnover. We measured the cell cycle and S-phase duration of myogenic cells in the fast myotomal muscle of two closely related Harpagifer species by cumulative S-phase labelling with 5-bromo-2′-deoxyuridine (BrdU). Harpagifer antarcticus is a stenothermal species from the Antarctic peninsula (experiencing temperatures of -2°C to +1°C) and Harpagifer bispinis is a eurythermal species from the Beagle Channel, Tierra del Fuego (living at +4°C in winter and up to 11°C in summer). Specific growth rates in the adult stages studied were not significantly different from zero. Myogenic progenitor cells were identified using an antibody against c-met. Seventy-five percent of the c-met+ve cells were in a proliferative state in both species. Cell cycle time was 150 h at 5°C and 81.3 h at 10°C in H. bispinis (Q10=3.4). Cell cycle duration was 35% shorter in H. antarcticus at 0°C (111 h) than in H. bispinis at 5°C. The predicted cell cycle time for H. bispinis at 0°C (based on the Q10 relationship) was 277 h, which was more than double that measured for the Antarctic species at this temperature. The results obtained are compatible with an evolutionary adjustment of cell cycle time for function at low temperature in the Antarctic species.
The Contribution of Badgers to Confirmed Tuberculosis in Cattle in High-Incidence Areas in England

The role of badgers in the transmission and maintenance of bovine tuberculosis (TB) in British cattle is widely debated as part of the wider discussions on whether badger culling and/or badger vaccination should play a role in the government’s strategy to eradicate cattle TB. The key source of information on the contribution from badgers within high-cattle-TB-incidence areas of England is the Randomised Badger Culling Trial (RBCT), with two analyses providing estimates of the average overall contribution of badgers to confirmed cattle TB in these areas. A dynamical model characterizing the association between the estimated prevalence of Mycobacterium bovis (the causative agent of bovine TB) among badgers culled in the initial RBCT proactive culls and the incidence among sympatric cattle herds prior to culling is used to estimate the average overall contribution of badgers to confirmed TB herd breakdowns among proactively culled areas. The resulting estimate based on all data (52%) has considerable uncertainty (bootstrap 95% confidence interval (CI): 9.1-100%). Separate analyses of experimental data indicated that the largest estimated reduction in confirmed cattle TB achieved inside the proactive culling areas was 54% (overdispersion-adjusted 95% CI: 38-66%), providing a lower bound for the average overall contribution of badgers to confirmed cattle TB. Thus, taking into account both results, the best estimate of the average overall contribution of badgers is roughly half, with 38% being a robustly estimated lower bound. However, the dynamical model also suggested that only 5.7% (bootstrap 95% CI: 0.9-25%) of the transmission to cattle herds is badger-to-cattle with the remainder of the average overall contribution from badgers being in the form of onward cattle-to-cattle transmission. These estimates, confirming that badgers do play a role in bovine TB transmission, inform debate even if they do not point to a single way forward.
18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms Is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture

Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of 18F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the 18F-FDG–positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no 18F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture. Methods: Biopsies of the AAA wall were obtained from patients with no 18F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site positive for uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography. Results: The sites of the aneurysmal wall with a positive 18F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein. Conclusion: Positive 18F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC in the media and alterations of the expression of genes involved in the remodeling of adventitia and collagen degradation potentially participate in the weakening of the aneurysmal wall preceding rupture.
Where is the comfort in comfort foods? Mechanisms linking fat signaling, reward, and emotion

Food in general, and fatty foods in particular, have obtained intrinsic reward value throughout evolution. This reward value results from an interaction between exteroceptive signals from different sensory modalities, interoceptive hunger/satiety signals from the gastrointestinal tract to the brain, as well as ongoing affective and cognitive processes. Further evidence linking food to emotions stems from folk psychology (‘comfort foods’) and epidemiological studies demonstrating high comorbidity rates between disorders of food intake, including obesity, and mood disorders such as depression.
Quantification of recirculation by thermodilution during venovenous extracorporeal membrane oxygenation.

PURPOSE The aim of this study was to determine whether recirculation could be quantified by a thermodilution technique during venovenous (VV) extracorporeal membrane oxygenation (ECMO) in a rabbit model. METHODS Five New Zealand white rabbits, mean weight, 4.5 (range, 3.7 to 5.7) kg, were anesthetized, instrumented, cannulated with a double-lumen catheter, and placed on VV ECMO. Serial injections of ice-cold saline were performed at the arterial arm of the circuit, and the resultant temperature change at various pump flows was measured at the venous arm of the circuit using a thermistor-tipped catheter and a cardiac output computer. Results were compared with the respective 100% recirculation measured with all the circuit flow passing through the bridge. RESULTS Using linear regression, recirculation percentage could be calculated as: 19 + 0.1 x pump flow (R2 = 0.81, P < .005). Recirculation correlated positively with pump flow. Variability between results at each flow was less than 10%. CONCLUSIONS Recirculation can be quantified during VV ECMO by measuring the change in temperature in the venous arm using a cardiac output computer after injection of a known quantity of ice-cold saline in the arterial side of the circuit. The effect of interventions to reduce recirculation can be assessed conveniently and reliably.
Effect of α-Tocopherol on the Cardiac Antioxidant Defense System and Atherogenic Lipids in Cigarette Smoke-Inhaling Mice

The present study was designed to evaluate the role ofα -tocopherol (AT) on the cardiac antioxidant defense system and atherogenic lipid profile in cigarette smoke (CS)-inhaling mice. CS exposure for 10 wk resulted in an increase in the levels of lipid peroxidation (LPO) and reduction in reduced glutathione (GSH) levels in heart. Supplementation with AT reduced LPO and restored GSH levels to almost those of normals. The activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) increased after CS inhalation. However, supplementation with AT resulted in reversing the increase in GSH-Px and GR. The activity of superoxide dismutase (SOD) remained unaltered in all the groups studied. Levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) increased, whereas high-density lipoprotein cholesterol (HDL-C) levels decreased in serum following CS inhalation. Supplementation with AT reduced the levels of LDL-C and TG. On the other hand, AT-fed animals showed an increase in HDL-C levels on CS exposure. Based on the results it appears that AT protects the heart from CS-induced peroxidative damage and has antiatherogenic properties.
Striatal dihydroxyphenylalanine decarboxylase and tyrosine hydroxylase protein in idiopathic Parkinson's disease and dominantly inherited olivopontocerebellar atrophy

We measured the levels of dopamine, tyrosine hydroxylase (TH) protein, and dihydroxyphenylalanine (DOPA) decarboxylase (DDC) protein in the striatum of 10 patients with idiopathic Parkinson's disease (PD) and 23 patients with dominantly inherited olivopontocerebellar atrophy (OPCA). The levels of dopamine were markedly reduced (2% of control) in the striatum of the patients with PD, whereas striatal dopamine in the patients with OPCA ranged from normal (<60% of control) to moderately reduced (20–60% of control) to severely depleted (<20% of control). Both TH and DDC protein levels were significantly lower than those of the controls in the striatum of all of the patients with PD and in the subgroup of patients with OPCA having severely depleted dopamine. In contradistinction, TH but not DDC protein levels were reduced in those patients with OPCA having moderately reduced dopamine levels. This suggests that in the early stage of nigrostriatal dopamine neurone degeneration, DDC levels may be less susceptible to neurodegenerative influences than is TH synthesis or, alternatively, DDC synthesis may be more aggressively upregulated. Unexpectedly, from the blot immunolabeling analysis an additional DDC‐immunoreactive band of slightly lower apparent molecular mass was detected in two of the patients with PD and in 12 of the patients with OPCA. This additional DDC band, which was not present in any of the control subjects, may reflect posttranslational modification(s) of DDC related to the neurodegenerative process.