TLR4 polymorphism and haplotype are associated with obesity and lipid profile in young population: a pilot study.

BACKGROUND: The single nucleotide polymorphisms in the TLR4 gene can decrease or increase the response to lipopolysaccharide, increasing the susceptibility to inflammatory diseases, affecting the expression or receptor function by inducing a low-grade chronic inflammatory response. PURPOSE: The objective of this study was to evaluate the association of SNPs - 2570 A > G (rs2737190), - 2081 G > A (rs10983755), 896 A > G (rs 4986790), and 1196 C > T (rs4986791) of the TLR4 gene with obesity and metabolic alterations in the young population. RESULTS: In this study, it was found that the carriers of the heterozygous genotype of the SNPs - 2081 G > A, 896 A > G, and 1196 C > T confer a higher risk of developing obesity (OR = 3.73, p = 0.018; OR = 5.66, p = 0.014, and OR = 8.95, p = 0.014, respectively). Also, with the lipid profile, the SNP - 2081 G > A was associated with total cholesterol (TC) ≥ 200 mg/dL (OR = 3.91, p = 0.020) and Kannel index > 3% (OR = 4.00, p = 0.008). The SNP 896 A > G was associated with LDL-c ≥ 100 mg/dL (OR = 3.64, p = 0.040) and Kannel index > 3% (OR = 4.33, p = 0.016), and the SNP 1196 C > T was associated with TC ≥ 200 mg/dL (OR = 4.37, p = 0.048), Castelli index > 4.5/> 5% (OR = 5.33, p = 0.016), and Kannel index > 3% (OR = 16.00, p = 0.001). Finally, the AGGT haplotype was associated with Castelli index > 4.5/> 5% (OR = 5.40, p = 0.015) and Kannel index > 3% (OR = 10.46, p < 0.001), and the AAAC haplotype was associated with obesity (OR = 3.56, p = 0.020), TC ≥ 200 mg/dL (OR = 4.04, p = 0.007), LDL-c ≥ 100 mg/dL (OR = 2.98, p = 0.030) and Kannel index > 3% (OR = 4.20, p = 0.002). CONCLUSION: The heterozygous genotype of the SNPs - 2081 G > A, 896 A > G and 1196 C > T of the TLR4 gene was associated with altered lipid profile and development of obesity in young university students of Guerrero State, Mexico.

Tibiotarsus bone characteristics and tibial dyschondroplasia incidence of broilers fed diets supplemented with leucine and valine.

Two experiments were conducted to study the effect of standardized ileal digestible (SID) leucine and valine levels on tibiotarsus bone characteristics and the incidence of tibial dyschondroplasia of broilers from day 1 to 21 (Experiment I) and day 21 to 42 post-hatch (Experiment II). Each experimental phase was evaluated independently. In both experiments, a total of 1,500 one-day-old Cobb 500 male broiler chickens were distributed in a completely randomized design 5 × 5 factorial arrangement for a total of 25 treatments. The SID leucine and valine levels were ranged from 10.0 to 19.6 g/kg, and 6.0 to 12.0 g/kg from day 1 to 21 post-hatch, respectively, while day 21 to 42 post-hatch ranged from 10.0 to 18.0 g leucine/kg, and 5.2 to 11.2 g valine/kg. Serum calcium and phosphorus, bone concentrations of calcium, phosphorus and ash, diameter and Seedor index of the tibiotarsus were not affected (p > .05) by the treatments at 21 or 42 days of age. There was an interaction (p ≤.06) between the SID levels of leucine and valine on tibiotarsus breaking strength at 21 days, but not at 42 days of age (p > .05). Tibiotarsus breaking strength was maximized in broilers from day 1 to 21 with the dietary levels of leucine and valine at 14.2 and 9.0 g/kg respectively. Dietary leucine levels reduced linearly (p < .05) the hypertrophic zone of tibiotarsus cartilage at 21 days of age. Therefore, leucine and valine supplementation interact positively on bone strength of broilers from day 1 to 21 post-hatch. Leucine can be a useful amino acid for reducing the hypertrophic cartilage zone in broilers from day 1 to 21, but not from day 21 to 42 post-hatch.

Comparative analysis of autoantibodies targeting peptidylarginine deiminase type 4, mutated citrullinated vimentin and cyclic citrullinated peptides in rheumatoid arthritis: associations with cytokine profiles, clinical and genetic features.

Antibodies against cyclic citrullinated peptides (anti-CCP) are widely used for diagnosis of rheumatoid arthritis (RA). We performed a comparative analysis of antibodies targeting the citrullinating enzyme peptidylarginine deiminase type 4 (anti-PAD4) and mutated citrullinated vimentin (anti-MCV) with anti-CCP autoantibodies in RA patients and examined their relationships with clinical parameters, cytokine profiles and the PADI4 gene. Autoantibodies were examined by enzyme-linked immunosorbent assay (ELISA) in sera of 170 RA patients and 103 controls. Cytokine profiles were measured using a multiplex system. PADI4 polymorphisms (89 G > A, 90 T > C and 92 G > C) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Anti-PAD4, anti-MCV and anti-CCP autoantibodies were detected in 24, 61 and 74% of RA patients, respectively. Positive correlations were observed between anti-PAD4 and disease duration; anti-CCP and erythrocyte sedimentation rate (ESR); anti-MCV and ESR and C-reactive protein. Anti-MCV antibodies were associated with high disease activity score 28 (DAS-28) in early RA. Concentrations of T helper type 1 (Th1) [tumour necrosis factor (TNF)-α, interleukin (IL)-12, IL-2, IL-1ß], Th2 (IL-4, IL-6, IL-10, IL-13) and Th17 (IL-17) cytokines were higher in RA than in controls. Th2 and, to a lesser extent, Th1-related cytokines, showed positive correlations with anti-MCV and anti-CCP. The GTG haplotype in PADI4 was associated with anti-CCP and anti-MCV, but not anti-PAD4 antibodies. In conclusion, anti-PAD4 antibodies are detected mainly in established RA, which is in contrast to the early detection of antibodies against citrullinated peptide/proteins (ACPAs). Among autoantibodies, anti-MCV appear to perform better as markers of disease activity. Furthermore, anti-CCP and anti-MCV are associated genetically with the citrullinating enzyme PAD4 and are related strongly to Th1 and Th2 cytokines, suggesting a feed-forward loop between cytokines and ACPA production.

Effects of dietary supplementation of meat-type quail breeders with guanidinoacetic acid on their reproductive parameters and progeny performance.

This study was conducted to assess the effect of dietary supplementation of meat-type quail breeders with guanidinoacetic acid (GAA) on their reproductive parameters and progeny performance. Two hundred forty meat-type quails at 25 wk of age were distributed in a completely randomized design with 5 treatments and 8 replicates of 6 birds each. The treatments consisted of 5 dietary levels of GAA (0.00, 0.06, 0.12, 0.18, and 0.24%). The progenies from quail breeders were housed according to breeder treatments and fed a conventional diet based on corn and soybean meal without GAA supplementation. Dietary GAA levels did not affect (P > 0.05) the productivity of meat-type quail breeders, although the concentration of guanidinic compounds (creatine, GAA, and creatinine) in the eggs from the breeders increased linearly (P < 0.05) according to the increase in dietary GAA levels. The number of spermatozoa present in the vitelline membrane was not affected (P > 0.05) by the treatments, but there was a quadratic effect (P < 0.05) of the levels of GAA on fertility, embryonic mortality, and egg hatchability, with the best results estimated at 0.13, 0.15, and 0.14% GAA, respectively. The creatine levels of the pectoral muscle in newborn quails showed a quadratic effect (P ≤ 0.07), and the dietary GAA level of 0.11% was estimated to maximize the muscular creatine level in the progeny. There was a quadratic effect (P < 0.05) of GAA levels on weight gain and feed conversion of progeny at 35 d of age with an optimization point of 0.14% GAA for these variables. Dietary GAA supplementation of meat-type quail breeders increases the availability of creatine in eggs and muscle of progeny, which results in better reproductive parameters and better postnatal progeny performance.

Valine, isoleucine, arginine and glycine supplementation of low-protein diets for broiler chickens during the starter and grower phases.

1. Two experiments were performed to study the supplementation of valine, isoleucine, arginine and glycine (Val, Ile, Arg, Gly) in low-protein diets for broiler chickens in the starter (1-21 d; Exp. 1) and grower (22-42 d; Exp. 2) phases. 2. A low-crude protein (CP) diet was formulated to meet the requirements of all amino acids (AA) supplied by the control diet except for Val, Ile, Arg and Gly. The other experimental diets were obtained by the isolated or combined supplementation of the studied AA in the low-CP diet. 3. Growth, serum parameters and litter characteristics were taken in both of the experiments. Carcass measurements were taken in Experiment 2. 4. In the starter and grower phases, low-CP diets without supplementation resulted in birds with a poorer weight gain and feed conversion than those of the birds that received the control diet. 5. In the starter phase, individual supplementation with Val and Gly, but not Ile and Arg, restored the weight gain of the birds, while diets with the addition of Val + Gly, Val + Ile + Arg, Val + Ile + Gly and Val + Ile + Arg + Gly restored their feed conversion. 6. In the grower phase, weight gain was re-established at the same rate as the control diet for the diets supplemented with Val + Ile, Val + Ile + Arg, Val + Ile + Gly and Val + Ile + Arg + Gly. However, the feed conversion was restored only in birds that received the diet supplemented with all studied AA. 7. The supplementation of Val and Gly in low-CP diets was sufficient to avoid adverse effects in the performance and serum parameters of broilers in the starter phase. However, birds in the grower phase required the combined supplementation of Val, Ile, Arg and Gly, to prevent compromised performance.

Macrophage migration inhibitory factor (MIF): genetic evidence for participation in early onset and early stage rheumatoid arthritis.

Macrophage migration inhibitory factor (MIF) is an upstream pro-inflammatory cytokine that is associated with the pathogenesis of autoimmune inflammatory diseases including rheumatoid arthritis (RA). Two polymorphisms in the upstream region exist in the MIF gene and are associated with RA susceptibility or severity in different populations. In this case-control study, we investigated whether MIF polymorphisms are associated with RA susceptibility or activity in a western Mexican population .The relationship of MIF levels with clinical features of disease also was assessed. Genotyping of the -794 CATT5-8 (rs5844572) and the -173 G>C (rs755622) polymorphisms was performed by PCR and PCR-RFLP respectively on 226 RA patients and 210 healthy subjects. Serum MIF levels were determined by ELISA. We found a significant association between the -794 CATT5-8 6,7 MIF genotype with RA. Moreover, we detected an association between the -794 CATT7 allele with early onset RA. The -794 CATT7 and -173(*)C alleles, which are in linkage disequilibrium, were associated with high disease activity on RA patients. A positive correlation between circulating MIF levels and C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, anti-citrullinated protein/peptides antibodies and TNFα was detected. MIF levels appear to be associated with disease progression rather than disease activity, which is distinct from the established relationship between disease activity and TNFα levels. In conclusion, the MIF gene and protein are associated with RA in a western Mexican population, with a main contribution onto early onset and early stages of disease.

Endemic pemphigus foliaceus in the Peruvian Amazon.

BACKGROUND: Endemic pemphigus foliaceus (EPF) is an organ-specific blistering disease of the epidermis characterized by the presence of IgG autoantibodies, specifically desmoglein (Dsg)1. This condition has been reported particularly in Brazil, Colombia, Tunisia and Peru. AIM: To characterize the humoral response against Dsg1 and Dsg3 autoantibodies of patients with EPF from the Peruvian Amazon region. METHODS: Blood samples were collected from 16 patients with a clinical diagnosis of EPF, and tested using indirect immunofluorescence (IIF), immunoprecipitation and ELISA (for IgG and its subclasses against Dsg1 and IgG against Dsg3). RESULTS: Autoantibodies against the intercellular spaces were detected by IIF in 82.5% and 87.5% of patients, using normal human skin and monkey oesophagus, respectively. Sera from all patients immunoprecipitated recombinant Dsg1, and three serum samples immunoprecipitated recombinant Dsg3 (6.25%). Using ELISA, anti-Dsg1 antibodies were detected in 13 patients (81.25%), and both IgG1 and IgG2 antibodies against Dsg1 in 12 patients (75%). All patients were positive for IgG4 autoantibodies, and only one patient was positive for IgG3 autoantibodies (6.25%). Anti-Dsg3 antibodies were detected in five patients (31.25%). CONCLUSIONS: EPF from Peru shares epidemiological, clinical and immunological characteristics with other forms of EPF that have been described in South America.

Supplemental glycine and threonine effects on performance, intestinal mucosa development, and nutrient utilization of growing broiler chickens.

A study was conducted to evaluate Gly requirements in low-CP diets with different levels of digestible (dig) Thr, and their effects on performance, intestinal mucosal development, and nutrient utilization of broiler chickens from 21 to 35 d age. A total of 240 twenty-one-day-old Cobb-Vantress male broiler chickens were distributed in a completely randomized 4 × 2 factorial arrangement for a total of 8 treatments with 5 replicates of 6 birds each. The treatments consisted of 4 levels of Gly+Ser (1.47, 1.57, 1.67, or 1.77%) and 2 levels of dig Thr (0.70 or 0.77%, corresponding to 100 or 110% of Thr requirements, respectively). Common diets were fed to broilers until 20 d of age. At d 35, an interaction (P ≤ 0.01) was observed between the Gly+Ser and dig Thr levels for G:F. Glycine supplementation resulted in a linear increase (P < 0.05) in BW gain, G:F, intestinal mucin secretion, apparent digestibility of fat, and AME values of the experimental diets. Threonine levels greater than the levels required (0.77%) improved (P < 0.05) G:F and increased (P < 0.05) intestinal mucin secretion. However, intestinal morphometry and the number of goblet cells in the duodenum, jejunum, and ileum were not affected by the treatments. The dietary Gly+Ser level necessary to optimize G:F in low-CP diets containing 0.77% Thr for broiler chickens during growth was estimated to be 1.54%; however, this requirement may be greater than 1.77% in diets with 0.70% Thr. Supplemental Gly may be essential to support maximum performance for broiler chickens from 21 to 35 d of age when they are fed diets based exclusively on vegetable ingredients and with low protein levels. Glycine can directly or indirectly influence the proper function of the intestinal mucosa and improve dietary energy utilization.

Mutation detection and typing of polymorphic loci through double-strand conformation analysis.

Variations, such as nucleotide substitutions, deletions and insertions, within genes can affect the function of the gene product and in some cases be deleterious. Screening for known allelic variation is important for determining disease and gene associations. Techniques which target specific mutations such as restriction enzyme polymorphism and oligonucleotide probe or PCR primer reactivity are useful for the detection of specific mutations, but these techniques are not generally effective for the identification of new mutations. Approaches for measuring changes in DNA conformation have been developed, based on the principle that DNA fragments which differ in nucleotide composition exhibit different mobilities after separation by polyacrylamide gel electrophoresis (PAGE). Here we describe a conformation-based mutation detection system, double-strand conformation analysis (DSCA), which provides a simple means to detect genetic variants and to type complex polymorphic loci. We demonstrate the application of DSCA to detect genetic polymorphisms such as a single-nucleotide difference within DNA fragments of up to 979 base pairs in length. We present the application of DSCA in detecting four different mutations in the cystic fibrosis gene (CFTR) and 131 different alleles encoded by HLA class I genes.

Dietary glycine+serine responses of male broilers given low-protein diets with different concentrations of threonine.

1. The objective of this study was to determine the optimum glycine+serine (Gly+Ser) concentration in low-crude protein (CP) diets that have adequate or high concentrations of dietary threonine (Thr) for broiler chickens in the initial growth phase. 2. Treatments consisted of four concentrations of dietary Gly+Ser (18.4; 19.8; 21.2 and 22.6 g/kg) and two concentrations of dietary Thr (9.3 and 10.7 g/kg, corresponding to 100 and 115% of the required Thr, respectively). 3. At 21d, interactions were observed between dietary Gly+Ser and Thr concentrations for the feed conversion ratio, creatine content in the pectoral muscles and serum concentrations of uric acid. There was a quadratic effect of the concentrations of Gly+Ser in the diets with 9.3 g Thr/kg on the feed conversion ratio and creatine content in the pectoral muscles, with an optimisation concentration of 20.8 and 21.1 g Gly+Ser/kg, respectively. 4. Diets containing 10.7 g Thr/kg negatively affected the feed conversion ratio, relative breast weight, creatine content in the pectoral muscles, serum concentrations of uric acid and ammonia in poultry compared to diets containing 9.3 g Thr/kg. 5. The need for Gly+Ser in diets with low-protein concentration (190 g CP/kg) and adequate concentration of Thr (9.3 g/kg) is 20.8 g/kg for broilers in the 1- to 21-d phase.

Common variants in the CRP gene are associated with serum C-reactive protein levels and body mass index in healthy individuals in Mexico.

Variants in the C-reactive protein (CRP) gene have been found to be associated with various phenotypic traits. We evaluated the effect of four SNPs in the CRP gene on serum levels of protein and body mass index (BMI) in 150 unrelated Mexican subjects from 18 to 25 years old, without hypertension, non-overweight, and without inflammatory diseases, non-smoking and non-consumers of alcohol. Subjects were measured for BMI, waist circumference, blood pressure, and serum glucose and triglycerides. The identification of SNPs was performed by PCR-RFLP. Three of the four SNPs were associated with variation in serum levels of CRP, increased in TT (rs1130864) and GG (rs2794521) genotypes, and decreased in the AA genotype of rs1205. The TT genotype was associated with a significant increase in BMI (ß = 1.1 kg/m², P = 0.04). Two haplotypes were significantly associated with increased serum levels of CRP, but not with BMI. We conclude that variation in the CRP gene affects serum protein levels.

Commercially available amino acid supplementation of low-protein diets for broiler chickens with different ratios of digestible glycine+serine:lysine.

This work studied the effect of supplementing commercially available amino acids in low-protein diets using different ratios of digestible (dig) glycine+serine:lysine (Gly+Ser:Lys) on performance, serum parameters, feathering, and litter characteristics of broiler chickens during the starter period. A total of one thousand fifty 1-d-old Cobb-Vantress male chicks were distributed in a completely randomized experimental design into 6 treatments with 5 replicates of 35 birds each. The treatments were as follows: T1, control diet based on corn and soybean meal formulated with 22% CP (dig Gly+Ser:Lys ratio of 147); T2, diet with a 2% CP reduction, supplemented with Val (dig Gly+Ser:Lys ratio of 137); T3, similar to T2 with the addition of Gly (dig Gly+Ser:Lys ratio of 147); T4, diet with a 3% CP reduction, supplemented with Val, Ile, and Arg (dig Gly+Ser:Lys ratio of 127); and T5 and T6, similar to T4 with the addition of Gly (dig Gly+Ser:Lys ratios of 137 and 147, respectively). At 7 and 21 d, broilers that had received diets with a 3% CP reduction (19% CP) and a Gly+Ser:Lys ratio that was equivalent to 127 had lower G:F (P < 0.05) and lower total protein and albumin serum concentrations (P < 0.05) than those broilers that received the control feed. However, these parameters were restored to the same level as the control diet with an increase in the dig Gly+Ser:Lys ratio from 127 to 137 and 147. Diets with a 3% CP reduction (19% CP) resulted in litter with reduced (P < 0.05) nitrogen content and lower ammonia emission than the litter of broilers receiving the control diet. The treatments did not influence (P > 0.05) the feather length or feathering scores at 21 or 28 d of age. The supplementation of essential amino acids while maintaining dig Gly+Ser:Lys ratios at and above 137 allowed for a reduction in the dietary CP of 3% without undermining the performance, feathering or serum parameters of early stage broilers.

[Stem cells: implications in the development of brain tumors]. / Células madre: implicaciones en el desarrollo de tumores cerebrales.

Stem cells are characterized by their capacity for self-renewal, for giving rise to new cells in specific tissues, and for maintaining this capacity throughout the entire life of their host. Stem cells are pluripotent and maintain continuous production of neurons, astrocytes, and oligodendrocytes. Stem cells in brain tumors also proliferate, undergo self-renewal, and give rise to other poorly differentiated cells. Unlike non-tumor stem cells, tumor stem cells lack the normal mechanisms that regulate proliferation and differentiation, resulting in uncontrolled production and incomplete differentiation of tumor cells. Discovering the role of tumor stem cells in the brain has given us a new perspective about the molecular pathways involved in signaling and about oncogenesis in the central nervous system; it can also help us explain the high rate of recurrence of some tumors and the diffuse nature of glioblastomas. Ideally, this perspective can be expected to lead to better treatments. This article reviews the characteristics of non-tumor and tumor stem cells, emphasizing the importance of brain tumor stem cells in the pathogenesis of common brain tumors.

Combination of white matter hyperintensities and Aß burden is related to cognitive composites domain scores in subjective cognitive decline: the FACEHBI cohort.

BACKGROUND: To explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aß) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD). METHODS: Two hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI), 18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables. RESULTS: Adjusted multiple linear regression models showed that FreeSurfer (B - .245; 95% CI - .1.676, - .393, p = .016) and ß burden (SUVR) (B - .180; 95% CI - 2.140, - .292; p = .070) were associated with face-name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p = .070). There was non-significant interaction of these two factors on this same CCs domain score (p = .54). However, its cumulative effects on face-name associative performance indicated that those individuals with either higher WMH load or higher Aß burden showed the worst performance on the face-name associative memory CCs domain score. CONCLUSIONS: Our results suggest that increased WMH load and increased Aß are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention.

[Acute heart failure in patients over 70 years of age: Precipitating factors of decompensation]. / Insuficiencia cardiaca aguda en pacientes de 70 años o más: factores precipitantes de descompensación.

OBJECTIVES: Heart failure decompensation is the most common reason for hospitalization in persons over 65 years old. There is limited information on the prevalence of precipitating factors of heart failure decompensation in this population. In this study we prospectively examined the factors associated with decompensation of heart failure in patients over 70 years of age. MATERIAL AND METHODS: During the 36 months from January 2006 to December 2008, we included 386 patients over 70 years of age that were admitted through emergencies with these three criteria: Dyspnea (class III or IV of the New Yourk Heart Association), pulmonary edema and echocardiographic data of left ventricular systolic or diastolic dysfunction. RESULTS: The mean age of the patients was 82 years and 58.5% were female. Left ventricular systolic dysfunction was diagnosed in 41.2% of them. We identified one or more precipitating factors of heart failure decompensation in 89.6% of the patients. The most common were atrial tachyarrhythmia (22.3%), respiratory infection (21.2%), severe anemia (17.1%), acute renal failure (12.7%), severe hypoalbuminemia (11.4%) and acute coronary syndrome (9.1%). Fifty-two patients (13.5%) died. The variables independently associated with hospital mortality were acute renal failure, severe hypoalbuminemia, systolic blood pressure <110mmHg, white blood cell count >10.000 per mm³ and valvular heart disease. CONCLUSIONS: In most patients over 70 years of age hospitalized with acute heart failure it is possible to identify one or more precipitating factors of decompensation, some of which are independently associated with hospital mortality.

High leucine levels affecting valine and isoleucine recommendations in low-protein diets for broiler chickens.

Four experiments were conducted to estimate the optimal standardized ileal digestible (SID) level of branched-chain amino acids in low-protein diets during the starter, grower, and finisher periods, using the response surface methodology, and to study their effects on performance and mRNA expression of genes involved in the mechanistic target of rapamycin (mTOR) pathway of broiler chickens from 8 to 21 D of age. In experiments 1, 2, and 3, a total of 1,500 Cobb male broiler chickens were assigned to 15 diets of a central composite rotatable design (CCD) of response surface methodology containing 5 levels of SID Leu, Val, and Ile with 5 replicate pens of 20 birds each. A 3-factor, 5-level CCD platform was used to fit the second-order polynomial equation of broiler performance. In experiment 4, a total of 540 8-day-old Cobb male broiler chickens were distributed in a completely randomized 2 x 3 x 3 factorial arrangement with 2 SID Leu levels (1.28 or 1.83%), 3 SID Val levels (0.65, 0.90, or 1.20%), and 3 SID Ile levels (0.54, 0.79, or 1.09%) for a total of 18 treatments with 5 replicate cages of 6 birds each. High Leu levels impaired (P < 0.05) gain:feed when birds were fed marginal Val or Ile diets. However, gain:feed was restored when both Val and Ile were supplemented to reach adequate or high levels. High Leu levels increased (P < 0.05) mRNA expression of S6K1 and eEF2 genes only in birds fed high Ile levels. Dietary SID Leu, Val, and Ile levels required for gain:feed optimization in low-protein diets were estimated at 1.37, 0.94, and 0.87% during the starter period; 1.23, 0.82, and 0.75% during the grower period; and 1.15, 0.77, and 0.70% during the finisher phase, respectively. Higher Val and Ile levels are required to optimize the effect of Leu supplementation on mRNA expression of mTOR pathway genes in the pectoralis major muscle of broilers from day 1 to 21 after hatch.

A framework to bridge scales in distribution modeling of soil microbiota.

Creating accurate habitat suitability and distribution models (HSDMs) for soil microbiota is far more challenging than for aboveground organism groups. In this perspective paper, we propose a conceptual framework that addresses several of the critical issues holding back further applications. Most importantly, we tackle the mismatch between the broadscale, long-term averages of environmental variables traditionally used, and the environment as experienced by soil microbiota themselves. We suggest using nested sampling designs across environmental gradients and objectively integrating spatially hierarchic heterogeneity as covariates in HSDMs. Second, to incorporate the crucial role of taxa co-occurrence as driver of soil microbial distributions, we promote the use of joint species distribution models, a class of models that jointly analyze multiple species' distributions, quantifying both species-specific environmental responses (i.e. the environmental niche) and covariance among species (i.e. biotic interactions). Our approach allows incorporating the environmental niche and its associated distribution across multiple spatial scales. The proposed framework facilitates the inclusion of the true relationships between soil organisms and their abiotic and biotic environments in distribution models, which is crucial to improve predictions of soil microbial redistributions as a result of global change.

The -675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus, its clinical manifestations, and comorbidities in Mexican-Mestizo population.

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the -675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the -675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The -675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81-3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62-4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31-2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84-3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the -675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.

A potential inflammatory role of IL-31 in psoriatic arthritis: A correlation with Th17 cytokine profile.

The goals of our study were to determine the possible association of interleukin (IL)-31 with Th17 cytokine profile in serum and to quantify retinoic acid-related orphan receptor C (RORC) mRNA expression in psoriatic arthritis (PsA) patients. This cross-sectional study was conducted in 50 patients with PsA and 30 control subjects (CS) matched by age and gender. The cytokine serum levels were quantified by magnetic bead-based assay using the Bio-Plex MAGPIX system, and RORC mRNA expression was determined by quantitative polymerase chain reaction (qPCR). As a result, significant differences in IL-31 were observed between study groups (77.23 pg/mL in PsA vs 64.4 pg/mL in CS, P < 0.001) and Th17 cytokine profile serum levels (IL-17A: 6.36 pg/mL in PsA vs 2.97 pg/mL in CS, P = 0.02; IL-17F: 44.15 pg/mL in PsA vs 23.36 pg/mL in PsA, P = 0.01; IL-17E: 3.03 pg/mL in PsA vs 0.82 pg/mL in CS, P < 0.001; IL-21: 36.45 pg/mL in PsA vs 12.44 pg/mL in CS, P = 0.02); however, significant differences were not observed for IL-23 (31.2 pg/mL in PsA vs 53.26 pg/mL in CS, P = 0.58). Furthermore, positive correlations between IL-31 and Th17 cytokine profile serum levels were found (IL-17A: rs = 0.64, P < 0.001; IL-17F: rs = 0.73, P < 0.001; IL-17E: rs = 0.70, P < 0.001; IL-21: rs = 0.54, P = 0.002; IL-23: rs = 0.5, P < 0.01). Regarding RORC gene expression, the PsA group showed an increase of 6.85-fold compared to the CS group. We did not find any association between the serum levels of cytokines and RORC gene expression. In conclusion, in PsA, there are increased serum levels of IL-31, IL-17A, IL-17F, IL-17E, and IL-21, but not IL-23. Moreover, there was a positive correlation of IL-31 with the Th17 cytokine profile and a high RORC gene expression. Altogether, these findings suggest a proinflammatory contribution of IL-31 in close association with the Th17 cytokine profile in PsA.