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Candida species have been responsible for a high number of invasive infections worldwide. In this sense, Rottlerin has demonstrated a wide range of pharmacological activities. Therefore, this study aimed to evaluate the antifungal, antibiofilm and antivirulence activity of Rottlerin in vitro against Candida spp. and its toxicity and antifungal activity in vivo. Rottlerin showed antifungal activity against all yeasts evaluated, presenting Minimum Inhibitory and Fungicidal Concentration (MIC and MFC) values of 7.81 to > 1000 µg/mL. Futhermore, it was able to significantly inhibit biofilm production, presenting Biofilm Inhibitory Concentration (MICB 50 ) values that ranged from 15.62 to 250 µg/mL and inhibition of the cell viability of the biofilm by 50% (IC 50 ) from 2.24 to 12.76 µg/mL. There was a considerable reduction in all hydrolytic enzymes evaluated, with emphasis on hemolysin where Rottlerin showed a reduction of up to 20%. In the scanning electron microscopy (SEM) analysis, Rottlerin was able to completely inhibit filamentation by C. albicans. Regarding in vivo tests, Rottlerin did not demonstrate toxicity at the therapeutic concentrations demonstrated here and was able to increase the survival of C. elegans larvae infected. The results herein presented are innovative and pioneering in terms of Rottlerin's multipotentiality against these fungal infections., (© 2024. The Author(s).)

There is scarce information on the vibrational and thermal properties of small Ni clusters. Here, the outcomes of ab initio spin-polarized density functional theory calculations on the size and geometry effects upon the vibrational and thermal properties of Ni n (n = 13 and 55) clusters, are discussed. For theses clusters a comparison is presented between the closed shell symmetric octahedral (O h ) and the icosahedral (I h ) geometries. The results indicate that the I h isomers are lower in energy. Besides, ab initio molecular dynamics runs at T = 300K show that Ni 13 and Ni 55 clusters transform from their initial O h geometries towards the corresponding I h ones. For Ni 13 , we also consider the lowest energy less symmetric layered 1-3-6-3 structure, and the cuboid, recently observed experimentally for Pt 13 , which is competitive in energy but is unstable, as phonon analysis reveals. We calculate their vibrational density of states (νDOS) and heat capacity, and compare with the Ni FCC bulk counterpart. The characteristic features of the νDOS curves of these clusters are interpreted in terms of the clusters' sizes, the interatomic distance contractions, the bond order values as well as the internal pressure and strains of the clusters. We find that the softest possible frequency of the clusters is size and structure-dependent, being the smallest for the O h ones. We identify mostly shear, tangential type displacements involving mainly surface atoms for the lowest frequency of the spectra of both I h and O h isomers. For the maximum frequencies of these clusters the central atom shows anti-phase movements against groups of nearest neighbor atoms. An excess of heat capacity at low temperatures with respect to the bulk is found, while at high temperatures a constant limiting value, close but lower to the Dulong and Petit value, is determined., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the air and water contamination level and to identify the microbes isolated from a rodent facility located at the Federal University of Uberlândia, Minas Gerais, Brazil. Colony forming units (CFU) per milliliter was used for monitoring water quantitatively; CFU per cubic meter was used for air monitoring. The isolated colonies were identified for qualitative monitoring. Due to absence of specific parameters for these facilities, the results were analyzed according to Brazilian and international standards, depending on which best suited each sample. The mean total number of microorganisms in water ranged from 0.015 ± 0.02 to 0.999 ± 0.91 CFU/mL. The number of microorganisms in air ranged from 9.1 ± 4.6 to 351.56 ± 158.2 CFU/m³. Forty-one microorganisms identified in the samples obtained from the rodent facility were potentially pathogenic or opportunistic for animals and humans (e.g., Corynebacterium spp.). We concluded that the water and air samples were contaminated with potentially pathogenic or opportunistic microorganisms that can harm rodents and humans. On the basis of our observations, specific sanitary standards suitable for these facilities should be developed for controlling microbial contamination, which will prevent zoonosis and ensure the reliability of scientific results obtained from animal experiments.

Objectives: Periodontitis is a pathology resulting from complex interaction of microorganisms in the dental biofilm with the host's immune system. Increased use of antibiotics associated with their inappropriate use has increased resistance levels in anaerobic bacteria. Therefore, identifying new antimicrobial compounds, such as chalcones, is urgent. This study evaluates the antibacterial activity and the antibiofilm activity of 15 chalcones against the periodontopathogenic bacteria Prevotella nigrescens (ATCC 33563), P. oralis (ATCC 33269), Peptostreptococcus anaerobius (ATCC 27337), Actinomyces viscosus (ATCC 43146), Porphyromonas asaccharolytica (ATCC 25260), and Fusobacterium nucleatum (ATCC 25586)., Methods: The compounds were evaluated by minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) tests., Results: Compounds 1-6 showed good antibacterial and antibiofilm activities against most of the evaluated bacteria: MIC was lower than or equal to 6.25 μg/mL, biofilm biomass was reduced by 95%, and the compounds at concentrations between 0.78 and 100 μg/mL totally inhibited cell viability. Among the tested chalcones, 3 stood out: it was effective against all the bacteria, as revealed by the MIC and MBIC results., Conclusions: Our results have consolidated a base for the development of new studies on the effects of the tested chalcones as agents to combat and to prevent periodontitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The use of renal biopsy through laparoscopy is increasingly present both in human and veterinary medicine. However, both techniques require skill and training to make the operator capable to do it. The learning curve allows the quantitative and qualitative assessment of the number of attempts and minimum time for the surgical procedure. The objective included establish the learning curve for laparoscopy-guided kidney biopsy procedures in dog and pig corpses. Six dogs and six pigs corpses weighing less than 10 kg were used for this study. All corpses underwent kidney biopsy performed through laparoscopy. Twenty-four operators, two per animal, performed 20 renal biopsies each (10 for each kidney), with 480 collection-procedures in total. Duration and difficulty of the procedure and the biopsy sample quality were evaluated and statistical analysis was performed using a mixed regression model with a random effect of individuals and multivariate analysis of data. There were 91.5% of the samples that were adequate for evaluation. There was no significant difference in the number of glomeruli or cortex percentage considering the attempts in either species, demonstrating the operator's ability since first collection. Swine samples showed higher amounts of renal cortex than canine samples. The procedure duration was shorter as more attempts were performed in dogs and pigs. From the fourth repetition, the professional reached a plateau for the variable related to 'collection', and from the second, the professional presented uniform duration for 'sample storage'. Operators of the swine model acquired more agility than the dog ones. The variable 'difficulty' decreased as more repetitions were performed, reaching a plateau in the sixth attempt. Seven renal biopsies laparoscopy-guided are required for an operator to be considered 'capable' to perform the procedure in the referred species included. The learning curve for image-guided kidney biopsy procedures improves the implementation of this technique and benefits patients that undergo this procedure., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this study was to build a prediction model to discriminate precociously hantavirus infection from leptospirosis, identifying the conditions and risk factors associated with these diseases., Methods: A logistic regression model in which the response variable was the presence of hantavirus or leptospirosis was adjusted., Results: As a result, the method selected the following variables that influenced the prediction formula: sociodemographic variables, clinical manifestations, and exposure to environmental risks. All variables considered in the model presented statistical significance with a p<0.05 value. The accuracy of the model to differentiate hantavirus from leptospirosis was 88.7%., Conclusions: Concluding that the development of statistical tools with high potential to predict the disease, and thus differentiate them precociously, can reduce hospital costs, speed up the patient's care, reduce morbidity and mortality, and assist health professionals and public managers in decision-making.

Pellets refer to solid biofuels for heating and power. The pellet's integrity is of great relevant to ensure safe and effective transportation and storage, and comfort to stakeholders. Several materials that are supportive, whether organic and inorganic, to pellets exist. However, no work in the literature is linking making hybrid non-wood pellets with addition of residual biomass from distillation of cellulosic bioethanol, and this requires further investigations. Figuring out how effective this challenging agro-industrial residue could be for reinforcing non-wood pellets is accordingly the scientific point of this study focusing on management of waste and valorization of biomass. The pilot-scale manufacturing of hybrid pellets consisted of systematically pressing sugarcane bagasse with the lignocellulosic reinforcement at the mass ratios of 3:1, 1:1, and 1:3 on an automatic pelletizer machine at 200 MPa and 125 °C. Elemental contents of C and H, durability, and energy density all increased significantly from 50.05 to 53.50%, 5.95 to 7.80%, 95.90 to 99.55%, and 28.20 to 31.20 MJ kg -1 , respectively, with blending the starting material with the reinforcement at 1:3. Preliminary evidence of residual biomass from distillation of second-generation bioethanol capable of highly improving molecular flammable/combustible properties, mechanical stability, and fuel power of composite non-wood pellets exist.

The microorganisms that constitute the oral microbiome can cause oral diseases, including dental caries and endodontic infections. The use of natural products could help to overcome bacterial resistance to the antimicrobials that are currently employed in clinical therapy. This study assessed the antimicrobial activity of the Copaifera pubiflora oleoresin and of the compounds isolated from this resin against oral bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays provided values ranging from 6.25 to > 400 μg/mL for the C. pubiflora oleoresin and its isolated compounds. The fractional inhibitory concentration index (FICI) assay showed that the oleoresin and chlorhexidine did not act synergistically. All the tested bacterial strains formed biofilms. MICB 50 determination revealed inhibitory action: values varied from 3.12-25 μg/mL for the oleoresin, and from 0.78 to 25 μg/mL for the ent-hardwickiic acid. Concerning biofilm eradication, the C. pubiflora oleoresin and hardwickiic acid eradicated 99.9 % of some bacterial biofilms. Acid resistance determination showed that S. mutans was resistant to acid in the presence of the oleoresin and ent-hardwickiic acid at pH 4.0, 4.5, and 5.0 at all the tested concentrations. Analysis of DNA/RNA and protein release by the cell membrane demonstrated that the oleoresin and hardwiickic acid damaged the bacterial membrane irreversibly, which affected membrane integrity. Therefore, the C. pubiflora oleoresin and ent-hardwickiic acid have potential antibacterial effect and can be used as new therapeutic alternatives to treat oral diseases such as dental caries and endodontic infections., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Schistosomiasis control in endemic areas depends on several factors, including chemotherapy, snail control and adequate sanitation. In this context, the employment of compounds isolated from plants is an important issue regarding infection and snail control. The aim of this study was therefore to evaluate the effects of curcumin (CUR), a compound isolated from Curcuma longa, against snails and embryos of Biomphalaria glabrata, which is the most important intermediate host of schistosomiasis in the Americas, as well as in cercariae, the infecting larval stage of Schistosoma mansoni., Results: CUR presented high activity against B. glabrata embryos and moderate activity against newborn and adult snails. The lethal concentration (LC 50 ) values after being exposed for 24 h and evaluated for 7 days were 6.54 (95% confidence interval (CI) 5.86-7.30) μg mL -1 for the embryos and 42.29 (95% CI 33.82-52.87) μg mL -1 and 87.69 (95% CI 68.82-111.7) μg mL -1 for the newborn and adult snails, respectively. Moreover, CUR inhibited the development of embryos and egg hatching, and decreased the fecundity rates of adult snails. CUR also demonstrated cercaricidal activity with LC 50 values lower than 10 μg mL -1 at 1, 3, 6, 9 and 12 h, respectively., Conclusion: Our data show that CUR has potential molluscicidal and cercaricidal activities. Moreover, as a nutraceutical compound that is toxic to both invertebrate host and parasite, CUR has the potential to be explored as a safe new agent to combat schistosomiasis. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

The discarded solutions by the chemical nickel industry have high amounts of nickel, this is why they are considered hazardous wastes for the health and the environment. On the other side, Ni particles can have potential applications in the developing of magnetorheological fluids currently being used to improve the performance of mechanical devices. The present study raises the treatment of a residual effluent from a chemical nickel industry by applying a chemical precipitation which uses sodium hypophosphite as a reducer, and varying the order of the reagents involved in the conditioning of the reaction with respect to the reducer. The recovered solids were studied using different material characterization techniques to recognize the chemical composition (X-Ray Fluorescence, Inductively Coupled Plasma Mass Spectrometry), crystallinity and morphology (X-Ray Diffraction, Scanning Electron Microscope), surface charge and size distribution (Dynamic Light Scattering). By the chemical reduction treatment it was possible to decrease the amount of nickel in the residual between 97.25% and 99.50%, obtaining Ni particles that were then tested to be used in magnetic fluids. To this purpose a suspension was prepared by mixing the Ni particles with silicone oil in a constant solid/liquid ratio, and the rheological behavior of this suspension was evaluated as a function of the magnetic field and the deformation applied, revealing an interesting magnetorheological behavior., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hemodialysis, which is a kidney failure treatment that uses hemodialysis machine, dialyzer, dialysis solution, catheters, and needles, favors biofilm formation. This study evaluates whether Aspergillus, Candida, and Fusarium can form biofilm in dialysis fluids. Biofilms were grown in 96-well microplates containing solutions (acid and basic) consisting of dialysate, dialysate per se, or dialysate plus glucose as culture medium. The biofilms were incubated at 30 °C for 72 h, quantified by the violet crystal methodology, and visualized by transmission electron microscopy. All the fungi formed biomass in all the tested solutions. However, Bonferroni analysis revealed that the dialysate facilitated Aspergillus biomass development, whereas the dialysate and dialysate with glucose provided similar Fusarium oxysporum biomass development. Candida parapsilosis development was favored in biofilms grown in basic electrolytic solution. Electron micrographs of biofilms that grew on catheters after 72 h showed that Aspergillus formed abundant hyphae; the extracellular matrix was visible on the surface of some hyphae when Aspergillus was grown in the dialysate. A multilayered hyphal structure emerged when F. oxysporum biofilms were incubated in the dialysate with glucose. C. parapsilosis biofilm growth in basic solution elicited a dense network of yeasts and pseudohyphae as well as the extracellular matrix; the biofilm was attached across the catheter length. This study may contribute to the formulation of new strategies to monitor biofilm formation and to increase knowledge associated with fungal biofilms in the dialysis environment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Foodborne diseases (FBDs) are a serious public health concern worldwide. In this scenario, preservatives based on natural products, especially plants, have attracted researchers' attention because they offer potential antimicrobial action as well as reduced health impact. The genus Copaifera spp., which is native of tropical South America and West Africa, contains several species for which pharmacological activities, including antibacterial effects, have been described. On the basis of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), antibiofilm activity (inhibition and eradication), preservative capacity, and Ames test, we evaluated the antibacterial, preservative, and mutagenic potential of Copaifera spp. oleoresins against the causative agents of FBDs. The Copaifera duckei, Copaifera reticulata, Copaifera paupera, and Copaifera pubiflora oleoresins displayed promising MIC/MBC values-from 12.5 to 100 μg/mL-against Staphylococcus aureus (American Type Culture Collection [ATCC] 29213), Listeria monocytogenes (ATCC 15313), and Bacillus cereus (ATCC 14579). C. duckei, C. reticulata, C. paupera, and C. pubiflora oleoresin concentrations ranging from 25 to 200 μg/mL and from 100 to 400 μg/mL inhibited biofilm formation and eradicated biofilms, respectively. The oleoresins did not exert mutagenic effects and had superior food preservative action to sodium benzoate (positive control). In conclusion, Copaifera oleoresins exhibit potential antibacterial activity and are not mutagenic, which makes them a promising source to develop novel natural food preservatives to inhibit foodborne pathogens.

Copaiba oil is widely used in medicine, but there are no reports regarding its application in ophthalmology. Therefore, the objective of this study was to evaluate the clinical, histopathological and toxicogenetic effects of eye drops containing 0.1 and 0.5% of Copaifera multijuga Hayne oil on superficial corneal ulcers induced with alkali in the left eye of rats. For histological analysis, the percent reduction in ulcers and thickness of the corneal epithelium and stroma were evaluated 48 and 72 h after ulcer induction. Additionally, neovascularization and polymorphonuclear infiltration were classified in the stroma. The bone marrow micronucleus test was used for toxicogenetic assessment. None of the animals exhibited clinical signs of immediate ocular discomfort after instillation and the eye drops were harmless to the ocular surface. There was a significant difference in percent ulcer reduction and corneal stroma thickness between animals treated with the C. multijuga eye drops and untreated animals with corneal injury and the negative control, respectively, suggesting a healing effect of the oleoresin. Analysis of the thickness of the corneal epithelium at the two time points showed that the eye drops formulated did not significantly reduce the damage caused by alkali. The same was observed for the treatments with the reference drugs. No difference in stromal neovascularization or inflammatory infiltration was observed between the treated groups. The toxicogenetic results revealed the absence of cytotoxicity and genotoxicity of the treatments. In conclusion, the C. multijuga eye drops did not cause damage to the ocular surface under the present experimental conditions and corneal epithelization was similar to the conventional treatments. These results indicate that eye drops containing C. multijuga oleoresin are a promising option for the treatment of superficial keratitis., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The aim of this study was to estimate heritability and predict breeding values for longevity among cows in herds of Nellore breed, considering the trait cow's age at last calving (ALC), by means of survival analysis methodology. The records of 11,791 animals from 22 farms were used. The variable ALC has been used by a criterion that made it possible to include cows not only at their first calving but also at their ninth calving. The criterion used was the difference between the date of each cow's last calving and the date of the last calving on each farm. If this difference was greater than 36 months, the cow was considered to have failed and uncensored. If not, this cow was censored, thus indicating that future calving remained possible for this cow. The survival model used for the analyses was the proportional hazards model, and the base risk was given by a Weibull distribution. The heritability estimate obtained was equal to 0.25. It was found that the ALC variable had the capacity to respond to selection for the purpose of increasing the longevity of the cows in the herds.

Intense selection among broilers, especially for performance and carcass traits, currently favors locomotion problems and bone resistance. Conducting studies relating to development and growth of bone tissue in broilers is necessary to minimize losses. Thus, genetic parameters were estimated for a broiler population's phenotypic traits such as BW at 42 d of age (BW42), chilled femur weight (CFW) and its yield (CFY), and femur measurements: calcium, DM, magnesium, phosphorus, and zinc content; breaking strength; rigidity; length; and thickness. Variance components were estimated through multitrait analyses using the restricted maximum likelihood method. The model included a fixed group effect (sex and hatch) and additive and residual genetic random effects. The heritability estimates we obtained ranged from 0.10 ± 0.05 to 0.50 ± 0.08 for chilled femur yield and BW42, respectively, and indicated that the traits can respond to the selection process, except for CFY, which presented low-magnitude heritability coefficients. Genetic correlation estimates between breaking strength, rigidity, and traits related to mineral content indicated that selection that aims to improve the breaking strength resistance of the femur is highly correlated with mineral content. Given the genetic correlation estimates between BW42 and minerals, it is suggested that in this population, selection for BW42 can be performed with greater intensity without affecting femoral integrity., (© 2015 Poultry Science Association Inc.)

RNA conformation plays a significant role in stability, ligand binding, transcription, and translation. Single nucleotide variants (SNVs) have the potential to disrupt specific structural elements because RNA folds in a sequence-specific manner. A riboSNitch is an element of RNA structure with a specific function that is disrupted by an SNV or a single nucleotide polymorphism (SNP; or polymorphism; SNVs occur with low frequency in the population, <1%). The riboSNitch is analogous to a riboswitch, where binding of a small molecule rather than mutation alters the structure of the RNA to control gene regulation. RiboSNitches are particularly relevant to interpreting the results of genome-wide association studies (GWAS). Often GWAS identify SNPs associated with a phenotype mapping to noncoding regions of the genome. Because a majority of the human genome is transcribed, significant subsets of GWAS SNPs are putative riboSNitches. The extent to which the transcriptome is tolerant of SNP-induced structure change is still poorly understood. Recent advances in ultra high-throughput structure probing begin to reveal the structural complexities of mutation-induced structure change. This review summarizes our current understanding of SNV and SNP-induced structure change in the human transcriptome and discusses the importance of riboSNitch discovery in interpreting GWAS results and massive sequencing projects., (© 2015 The Authors. WIREs RNA published by Wiley Periodicals, Inc.)

Objective: To identify novel genetic causes of syndromic hearing loss in Brazil., Design: To map a candidate chromosomal region through linkage studies in an extensive Brazilian family and identify novel pathogenic variants using sequencing and array-CGH., Study Sample: Brazilian pedigree with individuals affected by BO syndrome characterized by deafness and malformations of outer, middle and inner ear, auricular and cervical fistulae, but no renal abnormalities., Results: Whole genome microarray-SNP scanning on samples of 11 affected individuals detected a multipoint Lod score of 2.6 in the EYA1 gene region (chromosome 8). Sequencing of EYA1 in affected patients did not reveal pathogenic mutations. However, oligonucleotide-array-CGH detected a duplication of 71.8Kb involving exons 4 to 10 of EYA1 (heterozygous state). Real-time-PCR confirmed the duplication in fourteen of fifteen affected individuals and absence in 13 unaffected individuals. The exception involved a consanguineous parentage and was assumed to involve a different genetic mechanism., Conclusions: Our findings implicate this EYA1 partial duplication segregating with BO phenotype in a Brazilian pedigree and is the first description of a large duplication leading to the BOR/BO syndrome.

ZFP36L2 protein destabilizes AU-rich element-containing transcripts and has been implicated in female fertility. In the C57BL/6NTac mouse, a mutation in Zfp36l2 that results in the decreased expression of a form of ZFP36L2 in which the 29 N-terminal amino acid residues have been deleted, ΔN-ZFP36L2, leads to fertilized eggs that arrest at the two-cell stage. Interestingly, homozygous ΔN-Zfp36l2 females in the C57BL/6NTac strain release 40% fewer eggs than the WT littermates (Ramos et al., 2004), suggesting an additional defect in ovulation and/or oocyte maturation. Curiously, the same ΔN-Zfp36l2 mutation into the SV129 strain resulted in anovulation, prompting us to investigate a potential problem in ovulation and oocyte maturation. Remarkably, only 20% of ΔN-Zfp36l2 oocytes in the 129S6/SvEvTac strain matured ex vivo, suggesting a defect on the oocyte meiotic maturation process. Treatment of ΔN-Zfp36l2 oocytes with a PKA inhibitor partially rescued the meiotic arrested oocytes. Furthermore, cAMP levels were increased in ΔN-Zfp36l2 oocytes, linking the cAMP/PKA pathway and ΔN-Zfp36l2 with meiotic arrest. Since ovulation and oocyte maturation are both triggered by LHR signaling, the downstream pathway was investigated. Adenylyl cyclase activity was increased in ΔN-Zfp36l2 ovaries only upon LH stimulation. Moreover, we discovered that ZFP36L2 interacts with the 3'UTR of LHR mRNA and that decreased expression levels of Zfp36l2 correlates with higher levels of LHR mRNA in synchronized ovaries. Furthermore, overexpression of ZFP36L2 decreases the endogenous expression of LHR mRNA in a cell line. Therefore, we propose that lack of the physiological down regulation of LHR mRNA levels by ZFP36L2 in the ovaries is associated with anovulation and oocyte meiotic arrest.

Perturbations in immune processes are a hallmark of a number of autoimmune and inflammatory disorders. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an inflammatory disorder with possible autoimmune correlates, characterized by reduced NK cell activity, elevations in regulatory T cells (Tregs) and dysregulation in cytokine levels. The purpose of this article is to examine innate and adaptive immune cell phenotypes and functional characteristics that have not been previously examined in CFS/ME patients. Thirty patients with CFS/ME and 25 non-fatigued controls were recruited for this study. Whole blood samples were collected from all participants for the assessment of cell phenotypes, functional properties, receptors, adhesion molecules, antigens and intracellular proteins using flow cytometric protocols. The cells investigated included NK cells, dendritic cells, neutrophils, B cells, T cells, γδT cells and Tregs. Significant changes were observed in B-cell subsets, Tregs, CD4(+)CD73(+)CD39(+) T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-α and IFN-γ in the CFS/ME patients in comparison with the non-fatigued controls. Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation in CFS/ME and these may have similarities to a number of autoimmune disorders.

1. objective of the present study was to estimate heritability for hatch weight (HW), body weight at 90 (W90) and 180 (W180) d of age in Brazilian ostriches. 2. The heritability estimates were obtained through the restricted maximum likelihood method for an animal model. Least squares method was used to define possible fixed effects for consideration in the analysis model. 3. The estimates of heritability were 0.42 ± 0.05, 0.16 ± 0.04 and 0.24 ± 0.08 for HW, W90 and W180, respectively. 4. Heritability estimates showed that there are sufficient levels of additive genetic variation present in the traits studied, and these traits may respond to selection.

Objective: To assess the utility of the Newest Vital Sign (NVS) as a proxy for medication adherence in community-dwelling older adults., Design: Descriptive cross-sectional study., Setting: 12 adult day care centers in the Lisbon metropolitan area, Portugal, between March and May 2009., Participants: 100 white community-dwelling older adults., Intervention: Participants were administered the NVS, Single Item Literacy Screener (SILS), and self-reported Measure of Adherence to Therapy (MAT)., Main Outcome Measures: Health literacy and medication adherence., Results: The mean (±SD) age of the respondents was 73.3 ± 7.8 years and 71% were women. The NVS score was 0.81 ± 0.10 (of 6 possible points), and 95% of the respondents scored in the three lowest possible scores, indicating a notable floor effect. Age was found to be inversely correlated with NVS score (P = 0.003). The MAT score was 36.2 ± 4.7 (range 17-42). No statistically significant association between the NVS and level of education (P = 0.059 [Kruskal-Wallis]), gender (P = 0.700 [Mann-Whitney]), SILS (P = 0.167), or MAT (P = 0.379) was identified., Conclusion: The utility of the NVS as a proxy for medication adherence in community-dwelling older adults is limited because of a floor effect that hinders its predictive power for medication adherence.

In most studies on beef cattle longevity, only the cows reaching a given number of calvings by a specific age are considered in the analyses. With the aim of evaluating all cows with productive life in herds, taking into consideration the different forms of management on each farm, it was proposed to measure cow longevity from age at last calving (ALC), that is, the most recent calving registered in the files. The objective was to characterize this trait in order to study the longevity of Nellore cattle, using the Kaplan-Meier estimators and the Cox model. The covariables and class effects considered in the models were age at first calving (AFC), year and season of birth of the cow and farm. The variable studied (ALC) was classified as presenting complete information (uncensored = 1) or incomplete information (censored = 0), using the criterion of the difference between the date of each cow's last calving and the date of the latest calving at each farm. If this difference was >36 months, the cow was considered to have failed. If not, this cow was censored, thus indicating that future calving remained possible for this cow. The records of 11 791 animals from 22 farms within the Nellore Breed Genetic Improvement Program ('Nellore Brazil') were used. In the estimation process using the Kaplan-Meier model, the variable of AFC was classified into three age groups. In individual analyses, the log-rank test and the Wilcoxon test in the Kaplan-Meier model showed that all covariables and class effects had significant effects (P < 0.05) on ALC. In the analysis considering all covariables and class effects, using the Wald test in the Cox model, only the season of birth of the cow was not significant for ALC (P > 0.05). This analysis indicated that each month added to AFC diminished the risk of the cow's failure in the herd by 2%. Nonetheless, this does not imply that animals with younger AFC had less profitability. Cows with greater numbers of calvings were more precocious than those with fewer calvings.

The objective of this study was to fit growth curves using nonlinear and linear functions to describe the growth of ostriches in a Brazilian population. The data set consisted of 112 animals with BW measurements from hatching to 383 d of age. Two nonlinear growth functions (Gompertz and logistic) and a third-order polynomial function were applied. The parameters for the models were estimated using the least-squares method and Gauss-Newton algorithm. The goodness-of-fit of the models was assessed using R(2) and the Akaike information criterion. The R(2) calculated for the logistic growth model was 0.945 for hens and 0.928 for cockerels and for the Gompertz growth model, 0.938 for hens and 0.924 for cockerels. The third-order polynomial fit gave R(2) of 0.938 for hens and 0.924 for cockerels. Among the Akaike information criterion calculations, the logistic growth model presented the lowest values in this study, both for hens and for cockerels. Nonlinear models are more appropriate for describing the sigmoid nature of ostrich growth.

Egg production curves describe the laying patterns of hen populations over time. The objectives of this study were to fit the weekly egg production rate of selected and nonselected lines of a White Leghorn hen population, using nonlinear and segmented polynomial models, and to study how the selection process changed the egg-laying patterns between these 2 lines. Weekly egg production rates over 54 wk of egg production (from 17 to 70 wk of age) were measured from 1,693 and 282 laying hens from one selected and one nonselected (control) genetic line, respectively. Six nonlinear and one segmented polynomial models were gathered from the literature to investigate whether they could be used to fit curves for the weekly egg production rate. The goodness of fit of the models was measured using Akaike's information criterion, mean square error, coefficient of determination, graphical analysis of the fitted curves, and the deviations of the fitted curves. The Logistic, Yang, Segmented Polynomial, and Grossman models presented the best goodness of fit. In this population, there were significant differences between the parameter estimates of the curves fitted for the selected and nonselected lines, thus indicating that the effect of selection changed the shape of the egg production curves. The selection for egg production was efficient in modifying the birds' egg production curve in this population, thus resulting in genetic gain from the 5th to the 54th week of egg laying and improved the peak egg production and the persistence of egg laying.

We estimated genetic parameters for egg production in different periods by means of random regression models, aiming at selection based on partial egg production from a generation of layers. The production was evaluated for each individual by recording the number of eggs produced from 20 to 70 weeks of age, with partial records taken every three weeks for a total of 17 periods. The covariance functions were estimated with a random regression model by the restricted maximum likelihood method. A model composed of third-order polynomials for the additive effect, ninth-order polynomials for the permanent environment, and a residual variance structure with five distinct classes, was found to be most suitable for adjusting the egg production data for laying hens. The heritability estimates varied from 0.04 to 0.14. The genetic correlations were all positive, varying from 0.10 to 0.99. Selection applied in partial egg production periods will result in greater genetic profit for the adjacent periods. However, as the distance in time between periods increases, selection becomes less efficient. Selection based on the second period (23 to 25 weeks of age), where greater heritability was estimated, would note benefit the final egg-laying cycle periods.

Background: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an etiologically unexplained disorder characterised by irregularities in various aspects of the immunological function. Presently, it is unknown whether these immunological changes remain consistent over time. This study investigates Natural Killer (NK) cell cytotoxic activity, NK cell subsets (CD56brightCD16- and CD56dimCD16+) and cytokines, over the course of a12 month period in patients with CFS/ME., Methods: The participants in the study comprised 65 (47.2 ± 11.5 years) CFS/ME participants and 21 (45.2 ± 9.3 years) non-fatigued controls. Flow cytometry protocols were used to assess NK subsets and NK cytotoxic activity at various time points that included baseline (T1), 6 (T2) and 12 months (T3). Cytokine secretions were measured following mitogenic stimulation of peripheral blood mononuclear cells., Results: NK cytotoxic activity was significantly decreased in the CFS/ME patients at T1, T2 and T3 compared to the non-fatigued group. Additionally, in comparison to the non-fatigued controls, the CFS/ME group had significantly lower numbers of CD56brightCD16- NK cells at both T1 and T2. Interestingly, following mitogenic stimulation, cytokine secretion revealed significant increases in IL-10, IFN-γ and TNF-α at T1 in the CFS/ME group. A significant decrease was observed at T2 in the CFS/ME group for IL-10 and IL-17A while at T3, IL-2 was increased in the CFS/ME group in comparison to the non-fatigued controls. Overall cytotoxic activity was significantly decreased at T3 compared to T1 and T2. CD56brightCD16- NK cells were much lower at T2 compared to T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to T1 and T3., Conclusion: These results confirm decreases in immune function in CFS/ME patients, suggesting an increased susceptibility to viral and other infections. Furthermore, NK cytotoxic activity may be a suitable biomarker for diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study.

Background: Measuring health-related quality of life (QOL) helps evaluating the efficiency of a treatment and identifies problems with major impact on the patient's QOL. However, these measures are safer if assessed by generic and specific instruments together, where it is necessary to check for compatibility between these and avoid repetitions and contradictions between the domains., Objective: To describe the quality of life of hypertensive patients and to evaluate the compatibility of a specific instrument (MINICHAL) and a generic instrument (SF-36)., Methods: One hundred adult hypertensive under outpatient care were interviewed. The mean HRQOL as measured by MINICHAL was 6.64 (SD 6.04) in mental status and average of 5.03 (SD 4.11) in the state of somatic manifestations. The means for the instrument SF-36 were in ranking order: limitation due to physical aspects 47.3 (SD 42.9), vitality 57.4 (SD 19.7), limitation due to emotional aspects 58 (SD 44.7), functional capacity 58.7 (SD 27.8), pain 60.4 (SD 26.3), general health condition 60.7 (SD 22.7), mental health 66.8 (SD 22.1) and social aspects 78 (SD 26.1)., Results: The MINICHAL significantly correlated (p <0.001) with the SF-36 in all domains., Conclusion: The MINICHAL proved to be a useful tool in the assessment of HRQOL in patients with hypertension.

The zinc finger protein 36-like 2, Zfp36l2, has been implicated in female mouse infertility, because an amino-terminal truncation mutation (ΔN-Zfp36l2) leads to two-cell stage arrest of embryos derived from the homozygous mutant female gamete. Zfp36l2 is a member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins that can bind to transcripts containing AU-rich elements (ARE), resulting in deadenylation and destabilization of these transcripts. I show here that the mouse Zfp36l2 is composed of two exons and a single intron, encoding a polypeptide of 484 amino acids. I observed that ΔN-Zfp36l2 protein is similar to both wild-type Zfp36l2 and TTP (Zfp36) in that it shuttles between the cytoplasm and nucleus, binds to RNAs containing AREs, and promotes deadenylation of a model ARE transcript in a cell-based co-transfection assay. Surprisingly, in contrast to TTP, Zfp36l2 mRNA and protein were rapidly down-regulated upon LPS exposure in bone marrow-derived macrophages. The ΔN-Zfp36l2 protein was substantially more resistant to stimulus-induced down-regulation than the WT. I postulate that the embryonic arrest linked to the ΔN-Zfp36l2 truncation might be related to its resistance to stimulus-induced down-regulation.

The objectives of this paper were to identify the phenotypic egg-laying patterns in a White Leghorn line mainly selected for egg production, to estimate genetic parameters of traits related to egg production and to evaluate the genetic association between these by principal components analysis to identify trait(s) that could be used as selection criteria to improve egg production. Records of 54 wk of egg production from a White Leghorn population were used. The data set contained records of the length:width ratio of eggs at 32, 37, and 40 wk of age; egg weight at 32, 37, and 40 wk of age; BW at 54 and 62 wk of age; age at first egg; early partial egg production rate from 17 to 30 wk and from 17 to 40 wk of age; late partial egg production rate from 30 to 70 wk and from 40 to 70 wk of age; and total egg production rate (TEP). The estimates of genetic parameters between these traits were estimated by the restricted maximum likelihood method. Multivariate analyses were performed: a hierarchical cluster analysis, a nonhierarchical clustering analysis by the k-means method of weekly egg production rate to describe the egg-laying patterns of hens, and a principal components analysis using the breeding values of all traits. The highest heritability estimates were obtained for BW at 54 wk of age (0.68 ± 0.07) and age at first egg (0.53 ± 0.07). It is recommended that a preliminary clustering analysis be performed to obtain the population structure that takes into account the pattern of egg production, rather than the TEP, because hens may have the same final egg production with different patterns of egg laying. Early partial production periods were not good indicators for use in improving total egg production because these traits presented an overestimated genetic correlation with TEP because of the part-whole genetic correlation component. Egg production might be improved by selecting individuals based on TEP.

Studies estimating genetic parameters for reproductive traits in chickens can be useful for understanding and improvement of their genetic architecture. A total of 1276 observations of fertility (FERT), hatchability of fertile eggs (HFE) and hatchability of total eggs (HTE) were used to estimate the genetic and phenotypic parameters of 467 females from an F2 population generated by reciprocal crossing between a broiler line and a layer line, which were developed through a poultry genetics breeding program, maintained by Embrapa Swine and Poultry, Concordia, Santa Catarina, Brazil. Estimates of heritability and genetic and phenotypic correlations were obtained using restricted maximum likelihood calculations under the two-trait animal model, including the fixed effect of group (hatching of birds from the same genetic group) and the random additive genetic and residual effects. The mean percentages for FERT, HFE and HTE were 87.91 ± 19.77, 80.07 ± 26.81 and 70.67 ± 28.55%, respectively. The highest heritability estimate (h(2)) was 0.28 ± 0.04 for HTE. Genetic correlations for FERT with HFE (0.43 ± 0.17), HFE with HTE (0.98 ± 0.02) and FERT with HTE (0.69 ± 0.10) were positive and significant. Individuals with high breeding value for HTE would have high breeding values for HFE and FERT because of the high genetic association between them. These results suggest that HTE should be included as a selection criterion in genetic breeding programs to improve the reproductive performance of chickens, because HTE had the highest heritability estimate and high genetic correlation with FERT and HFE, and it is the easiest to measure.

The objective of this study was to estimate genetic and phenotypic correlations of body weight at 6 weeks of age (BW6), as well as final carcass yield, and moisture, protein, fat and ash contents, using data from 3,422 F2 chickens originated from reciprocal cross between a broiler and a layer line. Variance components were estimated by the REML method, using animal models for evaluating random additive genetic and fixed contemporary group (sex, hatch and genetic group) effects. The heritability estimates (h(2)) for BW6, carcass yield and percentage of carcass moisture were 0.31 ± 0.07, 0.20 ± 0.05 and 0.33 ± 0.07, respectively. The h(2) for the percentages of protein, fat and ash on a dry matter basis were 0.48 ± 0.09, 0.55 ± 0.10 and 0.36 ± 0.08, respectively. BW6 had a positive genetic correlation with fat percentage in the carcass, but a negative one with protein and ash contents. Carcass yield, thus, appears to have only low genetic association with carcass composition traits. The genetic correlations observed between traits, measured on a dry matter basis, indicated that selection for carcass protein content may favor higher ash content and a lower percentage of carcass fat.

Growth hormone (GH) is a commonly used drug aimed at improving sport performance. The aim of this study is to evaluate the immunomodulatory effects of short-term administration of recombinant GH (rhGH) in healthy young males. NK cell number, activity and phenotype, T cell number, CD4(+) (Th1/Th2) cytokine production of IL2, IL4, IL6, IL10, TNF-α and IFN-γ and CD4(+)/CD8(+) ratio with particular attention to the possible correlation to IGF-I production were investigated. 30 males (27 ± 9 years) were randomly assigned to placebo (n = 15) or drug (rhGH) 1 mg/day groups (n = 15) with daily injection for 7 days. IGF-I plasma concentration and flow cytometry data were generated at baseline and days 8, 15, 22 and 29 post injection. Data analysis used General Linear Model with repeated measures, Bonferroni correction factor and significance at p ≤ 0.05. Serum IGF-I levels (ng/mL) increased significantly (p ≤ 0.01) on day 8 (0.48 ± 0.78) after injections compared to baseline (0.31 ± 0.07) and days 15 (0.33 ± 0.06), 22 (0.29 ± 0.05) and 29 (0.29 ± 0.06). A significant time effect was noted in IL10 secretion (pg/mL) from day 15 (P = 35.14 ± 19.93, rhGH = 26.63 ± 16.39) to days 22 (P = 61.32 ± 20.41, rhGH = 74.99 ± 46.91) and 29 (P = 101.98 ± 67.25, rhGH = 107.74; ± 122.58). There was no correlation between IGF-I and NK activity, phenotype or number along with T lymphocyte number, CD4(+)/CD8(+) ratio or Th1 and Th2 cytokine production. In conclusion, cytokine secretion spectrum was not affected by short-term rhGH administration in young males.

Background: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is characterised by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers) in CFS/ME patients., Methods: We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK) and CD8(+) T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4(+) T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2), levels of NK phenotypes (CD56(bright) and CD56(dim)) and regulatory T cells expressing FoxP3 transcription factor., Results: Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4(+)CD25(+) T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8(+) T cells and NK phenotypes, in particular the CD56(bright) NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients., Conclusions: Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.

Introduction: It has been shown that growth hormone (GH) exerts regulatory effects on hemorheology and other metabolic functions. GH stimulates the production of insulin-like growth factor I (IGF-I) and GH-IGF-I system has profound effects on body fluid status. There are speculations that GH has become widely used as a performance enhancing drug among athletes of various sports. The present study evaluated the possible hemorheological effects of short term administration of human recombinant growth hormone (rhGH) in healthy young males., Methodology: Thirty young healthy males (27 ± 9) participated in a 29 days study where it was administered either 0.9% sodium chloride or 1 mg of human rhGH from day 1 to day 7. The participants were randomly assigned into either placebo (C) n = 15 or rhGH 1 mg/day (rhGH) group n = 15. This study evaluated plasma fibrinogen levels, red blood cell (RBC) aggregation, deformability and serum IGF-I levels between and within the groups along 29 days., Results: There was a significant increase in erythrocytes aggregation index post injection (day 8), in accordance to an increase in serum IGF-I.

Background: Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients., Methods: Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56(dim)CD16(+) and CD56(bright)CD16(-)) and NK cytotoxic activity. Erythrocyte aggregation, deformability and fibrinogen levels were also assessed., Results: CFS patients (n = 10) had significant decreases in neutrophil respiratory burst, NK cytotoxic activity and CD56(bright)CD16(-) NK phenotypes in comparison to healthy controls (n = 10). However, hemorheological characteristic, aggregation, deformability, fibrinogen, lymphocyte numbers and CD56(dim)CD16(+) NK cells were similar between the two groups., Conclusion: These results indicate immune dysfunction as potential contributors to the mechanism of CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function and phenotypes may be important diagnostic markers for CFS. The absence of rheological changes may indicate no abnormalities in erythrocytes of CFS patients.

Members of the tristetraprolin family of CCCH tandem zinc finger proteins bind to AU-rich elements in certain cellular mRNAs, leading to their deadenylation and destabilization. Studies in knock-out mice demonstrated roles for three of the family members, tristetraprolin, ZFP36L1, and ZFP36L2, in inflammation, chorioallantoic fusion, and early embryonic development, respectively. However, little is known about a recently discovered placenta-specific tristetraprolin family member, ZFP36L3. Tristetraprolin, ZFP36L1, and ZFP36L2 have been shown to shuttle between the nucleus and cytoplasm, using typical hydrophobic amino acid-rich nuclear export sequences, and nuclear localization sequences located within the tandem zinc finger domain. In contrast, we previously showed that green fluorescent protein-labeled ZFP36L3, expressed in HEK 293 cells, remained cytosolic, even in the presence of the nuclear export blocker leptomycin B. We show here that the conserved tandem zinc finger domain contains an active nuclear localization signal. However, the sequence corresponding to the nuclear export signal in the other family members was nonfunctional, and thus did not contribute to the cytosolic localization. The unique C-terminal repeat domain could override the activity of the nuclear localization sequence, preventing the import of ZFP36L3 into the nucleus. Immunostaining of mouse placenta demonstrated that ZFP36L3 was located only in the cytoplasm of trophoblast cells. Thus, in contrast to the other mammalian members of this protein family, ZFP36L3 is a "full-time" cytosolic protein, rather than a nucleocytoplasmic shuttling protein. The significance of this difference in subcellular localization to the physiology of placental trophoblast cells, where ZFP36L3 is selectively expressed, remains to be determined.

Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger (TZF) proteins can bind directly to AU-rich elements (ARE) in mRNA, causing deadenylation and destabilization of the transcripts to which they bind. We describe here a novel fourth mammalian member of the TTP protein family, designated ZFP36L3, which could also bind directly to ARE-containing RNAs and could promote the deadenylation and degradation of ARE-containing target RNAs. Zfp36l3 transcript expression was detected only in placenta and extraembryonic tissues in the mouse. It was expressed throughout development in the placenta and was particularly highly expressed in the cells of the labyrinthine layer of the trophoblastic placenta. Unlike the other family members, the expression of a ZFP36L3-green fluorescent protein fusion protein was entirely cytoplasmic when expressed in 293 cells, even in the presence of the CRM1-dependent nuclear export inhibitor leptomycin B. Zfp36l3 was located on the mouse X chromosome; a similar predicted gene was present on the rat X chromosome, but there was no evidence for a similar gene in humans. ZFP36L3 may thus be a rodent-specific or even murine-specific member of the TTP protein family. Its presumed role in placental physiology may be unique to rodents or murine rodents, but this role may be subsumed by other family members in nonrodents.

The CCCH tandem zinc finger protein, Zfp36l2, like its better-known relative tristetraprolin (TTP), can decrease the stability of AU-rich element-containing transcripts in cell transfection studies; however, its physiological importance is unknown. We disrupted Zfp36l2 in mice, resulting in decreased expression of a truncated protein in which the N-terminal 29 amino acids had been deleted (DeltaN-Zfp36l2). Mice derived from different clones of ES cells exhibited complete female infertility, despite evidence from embryo and ovary transplantation experiments that they could gestate and rear wild-type young. DeltaN-Zfp36l2 females apparently cycled and ovulated normally, and their ova could be fertilized; however, the embryos did not progress beyond the two-cell stage of development. These mice represent a specific model of disruption of the earliest stages of embryogenesis, implicating Zfp36l2, a probable mRNA-binding and destabilizing protein, in the physiological control of female fertility at the level of early embryonic development. This newly identified biological role for Zfp36l2 may have implications for maternal mRNA turnover in normal embryogenesis, and conceivably could be involved in some cases of unexplained human female infertility.

To evaluate the membrane expression of histocompatibility (HLA) class I (A-C) molecules on lymphomononuclear cells involved in the pathogenesis of type 1 diabetes, we studied 20 newly diagnosed Brazilian patients and 20 matched controls. The coexpression of HLA and cluster of differentiation (CD) molecules was evaluated by flow cytometry. Compared to controls, patients presented increased fluorescence intensity of HLA class I molecules on CD3+, CD4+ and CD8+ cells. Patients exhibiting the HLA-DQB1*0201 and/or DQB1*0302 alleles presented increased expression of class I molecules in relation to HLA-matched healthy controls. The increased HLA class I expression in subsets of T cells may be due to the proinflammatory profile of the disease as well as to the presence of diabetes susceptibility alleles.

Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins can bind directly to certain types of AU-rich elements (AREs) in mRNA. Experiments in TTP-deficient mice have shown that TTP is involved in the physiological destabilization of at least two cytokine mRNAs, those encoding tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. The two other known mammalian members of the TTP family, CMG1 and TIS11D, also contain ARE-binding CCCH tandem zinc finger domains and can also destabilize ARE-containing mRNAs. To investigate the effects of primary sequence on the subcellular localization of these proteins, we constructed green fluorescent protein fusions with TTP, CMG1, and TIS11D; these were predominantly cytoplasmic when expressed in 293 or HeLa cells. Deletion and mutation analyses revealed functional nuclear export signals in the amino terminus of TTP and in the carboxyl termini of CMG1 and TIS11D. This type of leucine-rich nuclear export signal interacts with the nuclear export receptor CRM1; abrogation of CRM1 activity resulted in nuclear accumulation of TTP, CMG1, and TIS11D. These proteins are thus nucleocytoplasmic shuttling proteins and rely on CRM1 for their export from the nucleus. Although TTP, CMG1, and TIS11D lack known nuclear import sequences, mapping experiments revealed that their nuclear accumulation required an intact tandem zinc finger domain but did not require RNA binding ability. These findings suggest possible roles for nuclear import and export in the regulation of cellular TTP, CMG1, and TIS11D activity.

The purpose of this study was to determine the effect of thymectomy on the number and activity of NK cells in the peripheral blood of children submitted to thymus removal. Twenty-three children, aged 4 to 48 months at thymectomy, whose thymus was fully removed to permit access to the heart for corrective surgery, were studied. Only children thymectomized during the first year of life had a decreased number of CD2+/CD3+, CD4+/CD16- , and CD8+/CD16- T subsets and an increase in the CD16-/CD56bright+ NK subset. In addition, the CD57-/CD16+ and CD57-/D56+ subsets which are shared by T and NK cells were increased. These findings associated with a tendency to increased NK activity suggest that the human thymus is partially involved in the control of the release of circulating T cells and may negatively modulate some NK subsets, as well as NK activity, during the first year of life but not later.

Background: Several surgical techniques such as the Ross operation or total correction of tetralogy of Fallot require incisions of the upper ventricular septum. Very few reports on the anatomy of the septal arteries of the pathologic heart can be found in the literature. To get a more precise knowledge of the large septal arteries in pathologic hearts, we have compared the anatomy of normal hearts with that of hearts with aortic valve disease and of tetralogy of Fallot., Methods: Twenty-six normal heart specimens (group A), 11 with aortic valve disease (group B), and 4 with tetralogy of Fallot (group C) were dissected., Results: In groups B and C a single large septal artery was always found. The large septal artery had the orientation previously described for normal hearts. Still, its course in the lower border of the anterior extension of the septomarginal trabecula was deeper. The anterior extension of the septomarginal trabecula was 4 +/- 3 mm deep in group A, 6 +/- 2 mm in group B, and 3 mm in group C. The interventricular septum was much thicker in groups B and C than in group A., Conclusions: The position of the large septal artery can be predicted from coronary angiography and from the morphology of the anterior extension of the septomarginal trabecula. Knowledge of its position can improve the safety of operations performed on the outflow of the interventricular septum.