Genetic and environmental factors influencing the human factor H plasma levels

Factor H is a plasma protein that plays a critical role in the regulation of complement activation in fluid phase and on cellular surfaces. Over the years numerous reports have illustrated the association of factor H deficiencies with chronic renal and infectious diseases. Plasma levels of factor H show a five-fold range of variation in humans (116–562 g/ml), which may also be relevant to disease susceptibility. To quantify the effects of the genetic and environmental factors responsible for the variation in the factor H plasma levels, we have applied variance-component methods to a family-based sample. Factor H plasma levels show an age-dependent increase (P<0.0001) and are decreased in smokers (P<0.0001). Interestingly, the heritability of the factor H trait is very high (h²=0.62±0.07; P<0.0001), indicating that 62% of the factor H phenotypic variance is due to the additive effects of genes. On this premise, we conducted a genome-wide linkage screen in order to identify genes regulating the factor H trait. Three genomic regions (1q32, 2p21–24 and 15q22–24) provided suggestive evidence of linkage (LOD scores 2.03, 2.15 and 2.00, respectively) with the plasma levels of factor H.     

Reflex control of intestinal gas dynamics and tolerance in humans

Intestinal transit of gas is normally adapted to the luminal gas load, but in some patients impaired transit may lead to gas retention and symptoms. We hypothesized that intestinal gas transit is regulated by reflex mechanisms released by segmental distension at various gut levels. In 24 healthy subjects, we measured gas evacuation and perception of jejunal gas infusion (12 ml/min) during simultaneous infusion of duodenal lipids mimicking the postprandial caloric load (Intralipid, 1 kcal/min). We evaluated the effects of proximal (duodenal) distension (n = 8), distal (rectal) distension (n = 8), and sham distension, as control (n = 8). Duodenal lipid infusion produced gas retention (366 +/- 106 ml) with low abdominal perception (1.5 +/- 0.8 score). Distension of either the duodenum or rectum during lipid infusion expedited gas transit and prevented retention (-120 +/- 164 and -124 +/- 162 ml retention, respectively; P < 0.05 vs. control). However, the tolerance to the intestinal gas load differed markedly, depending on the site of distension; perception remained low during rectal distension (2.6 +/- 0.7 score; not significant vs. control) but increased during duodenal distension (4.4 +/- 0.7 score; P < 0.05 vs. control). We conclude that focal gut distension, either at proximal or distal sites, accelerates gas transit, but the symptomatic response depends on the site of stimulation.     

Allozyme diversity in the tetraploid endemic Thymus loscosii (Lamiaceae)

BACKGROUND AND AIMS: Thymus loscosii (Lamiaceae) is a tetraploid perennial species endemic to the Ebro river basin (north-eastern Spain), which is included in the National Catalogue of Endangered Species. It is a tetraploid species (2n = 54), presumably an autotetraploid originated by the duplication of a 2n = 28 genome and the subsequent loss of two chromosomes. Allozyme electrophoresis was conducted to survey the levels and distribution of genetic diversity and to test the previous autopolyploid hypothesis for its origin. In addition, both in situ and ex situ conservation measures are proposed. METHODS: Eight populations were sampled for analysis by standard methods of starch gel electrophoresis, and six putative enzymatic loci were resolved (five consistently and one only partially). KEY RESULTS: Banding patterns exhibited no evidence of fixed heterozygosity and showed both balanced and unbalanced heterozygotes. In addition, most individuals showed a pattern consistent with the presence of three or four alleles at a single locus. High levels of genetic variability were found at population level (P = 85 %, A = 3.0, He = 0.422), in addition to a trend of an excess of heterozygotes. CONCLUSIONS: Allozyme data support the hypothesis that T. loscosii is an autotetraploid, and the high number of alleles at some loci may be due to repeated polyploidization events. The high values of genetic variation found in this species agree with those expected for tetraploids. The excess of heterozygotes may be due to some barriers to inbreeding (e.g. occurrence of gynodioecy) and/or selection for heterozygosity.     

Alfalfa leafcutting bee population dynamics, flower availability, and pollination rates in two Oregon alfalfa fields

Since the 1970s, it has become increasingly difficult for U.S. alfalfa seed producers to maintain Megachile rotundata (F.) populations used for alfalfa, Medicago sativa L., pollination. In 1998, we monitored M. rotundata population dynamics and foraging behavior, as well as alfalfa bloom and pollination rates in two fields in eastern Oregon. Despite marked differences in bee management, establishment was very similar in the two fields (approximately 0.5 females per nesting cavity) and lagged peak bloom by approximately 2 wk. Pollination rates increased from 0-10% in the first 3 wk to 80-90% in week 4-5. By then, M. rotundata females had difficulty finding untripped (nonpollinated) flowers and visited large numbers of already tripped or not fully matured flowers. M. rotundata progeny mortality was very high (54-78%). Estimated seed yields were similar in both fields. We contend similar seed yields, and improved bee production, could be accomplished with smaller bee populations, better timed with alfalfa bloom.     

Developmental Evolution: Torso — a Story with Different Ends?

The Torso pathway patterns the ends of the Drosophila embryo. Now, it has been found to control axis elongation in the short germ insect Tribolium. This result raises the issue of the ancestral function of the Torso pathway and its evolution.     

Associations between epicardial adipose tissue,subclinical atherosclerosis and high-density lipoprotein composition in type 1 diabetes

Background

The pathophysiology of cardiovascular complications in people with type 1 diabetes (T1DM) remains unclear. An increase in epicardial adipose tissue (EAT) and alterations in the composition of high-density lipoprotein (HDL) are associated with coronary artery disease, but information on its relationship in T1DM is very limited. Our aim was to determine the association between EAT volume, subclinical atherosclerosis, and HDL composition in type 1 diabetes.

Methods

Seventy-two long-term patients with T1DM without clinical atherosclerosis were analyzed. EAT volume and subclinical atherosclerosis were measured using cardiac computed tomography angiography. EAT was adjusted according to body surface to obtain an EAT index (iEAT). HDL composition was determined.

Results

The mean iEAT was 40.47?±?22.18 cc/m². The bivariate analysis showed positive associations of the iEAT with gender, age, hypertension, dyslipidemia, smoking, body mass index, waist circumference, insulin dose, and triglyceride (P?<?0.05). The iEAT correlated positively with small HDL, increased content of apolipoprotein (apo)A-II and apoC-III, and decreased content of apoE and free cholesterol. Multiple linear regression showed that age, apoA-II content in HDL, and waist circumference were independently associated with the iEAT. Fifty percent of the patients presented subclinical atherosclerotic lesions. These patients had a higher iEAT, and their HDL contained less cholesterol and more apoA-II and lipoprotein-associated phospholipase A2 than patients without subclinical atherosclerosis.

Conclusion

Alterations in the composition of HDL in TIDM are associated with increased iEAT and the presence of subclinical atherosclerosis. We propose that these abnormalities of HDL composition could be useful to identify T1DM patients at highest cardiovascular risk.

     

Calprotectin strongly and independently predicts relapse in rheumatoid arthritis and polyarticular psoriatic arthritis patients treated with tumor necrosis factor inhibitors: a 1-year prospective cohort study

Background

Calprotectin is a biomarker of disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and predicts relapse in juvenile idiopathic arthritis. Higher drug trough serum levels are associated with a good response in patients treated with tumor necrosis factor inhibitors (TNFi). Power Doppler ultrasound synovitis is predictive of relapse and structural damage progression in patients in clinical remission. The purpose of this study was to analyze the accuracy of serum calprotectin levels, drug trough serum levels (TSL), and power Doppler (PD) activity as predictors of relapse in RA and PsA patients in remission or with low disease activity receiving TNFi.

Methods

This was a longitudinal, prospective, 1-year single-center study of 103 patients (47 RA, 56 PsA) receiving TNFi in remission or with low disease activity (28-joint Disease Activity Score (DAS28)?≤?3.2). The predictive value of serum calprotectin, TNFi TSL, and PD were assessed using receiver operating characteristic (ROC) analyses. To illustrate the predictive performance of calprotectin, TNFi TSL, and PD score, Kaplan-Meier curves were constructed from baseline to relapse. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates and to fully adjust the association between calprotectin, TNFi TSL, and PD score with relapse. A generalized estimating equation model with an identity link for longitudinal continuous outcomes was used to assess the effect of covariates on TNFi TSL.

Results

Ninety-five patients completed 1 year of follow-up, of whom 12 experienced a relapse. At baseline, relapsers had higher calprotectin levels, lower TNFi TSL, and higher PD activity than nonrelapsers. ROC analysis showed calprotectin fully predicted relapse (area under the curve (AUC)?=?1.00). TNFi TSL and PD had an AUC of 0.790 (95% confidence interval (CI) 0.691–0.889) and 0.877 (95% CI 0.772–0.981), respectively. Survival analyses and log rank tests showed significant differences between groups according to calprotectin serum levels (p?<?0.001), TNFi TSL (p?=?0.004), and PD score (p?<?0.001). Univariate Cox regression models showed that time-to-remission/low disease activity (hazard ratio (HR)?=?1.17, p?<?0.001), calprotectin levels (HR?=?2.38, p?<?0.001), TNFi TSL (HR?=?0.47, p?=?0.018), and PD score (HR?=?1.31, p?<?0.001) were significantly associated with disease relapse. In the multivariate analysis, only baseline calprotectin levels independently predicted disease relapse (HR?=?2.41, p?=?0.002). The generalized estimating equation analysis showed that only disease activity by DAS28-erythrocyte sedimentation rate (ESR) was significantly associated with longitudinal changes in TNFi TSL (regression coefficient 0.26 (0.0676 to 0.0036), p?=?0.001).

Conclusion

Time-to-remission/low disease activity, calprotectin serum levels, TNFi TSL, and PD score were significantly associated with disease relapse. However, only baseline calprotectin serum levels independently predicted disease relapse in RA and PsA patients under TNFi therapy.