Whole Grain Rye Intake,Reflected by a Biomarker,Is Associated with Favorable Blood Lipid Outcomes in Subjects with the Metabolic Syndrome – A Randomized Study

Background and Aim

Few studies have explored the possible plasma cholesterol lowering effects of rye consumption. The aim of this secondary analysis in the SYSDIET study was to investigate the association between plasma alkylresorcinols (AR), a biomarker for whole grain wheat and rye intake, and blood lipid concentrations in a population with metabolic syndrome. Furthermore, we analyzed the associations between the AR C17∶0/C21∶0 ratio, a suggested marker of the relative intake of whole grain/bran rye, and blood lipid concentrations.

Methods

Participants were 30–65 years of age, with body mass index (BMI) 27–40 kg/m² and had metabolic syndrome. Individuals were recruited through six centers in the Nordic countries and randomized either to a healthy Nordic diet (ND, n = 93), rich in whole grain rye and wheat, as well as berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products, or a control diet (n = 65) for 18/24 weeks. Associations between total plasma AR concentration and C17∶0/C21∶0 homologue ratio and blood lipids were investigated in pooled (ND + control group) regression analyses at 18/24 weeks adjusted for baseline value for the dependent variable, age, BMI and statin use.

Results

When adjusted for confounders, total plasma AR at 18/24 weeks was not significantly associated with blood lipids but the AR ratio C17∶0/C21∶0 was inversely associated with LDL cholesterol concentrations (B (95% CI): −0.41 (−0.80 to −0.02)), log LDL/HDL cholesterol ratio (−0.20 (−0.37 to −0.03)), log non-HDL cholesterol (−0.20 (−0.37 to −0.03)), log apolipoprotein B (−0.12 (−0.24 to 0.00)) and log triglyceride concentrations (−0.35 (−0.59 to −0.12)).

Discussion

Increased proportion of whole grain rye, reflected by a biomarker, in the diet is associated with favorable blood lipid outcomes, a relationship that should be further investigated.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00992641","term_id":"NCT00992641"}}NCT00992641     

Grazed wet meadows are sink habitats for the southern dunlin (Calidris alpina schinzii) due to nest trampling by cattle

The effect of habitat management is commonly evaluated by measuring population growth, which does not distinguish changes in reproductive success from changes in survival or the effects of immigration or emigration. Management has rarely been evaluated considering complete life cycle of the target organisms, including also possible negative impacts from management. We evaluated the effectiveness of cattle grazing in the restoration of coastal meadows as a breeding habitat for small and medium‐sized ground‐nesting birds by examining the size and demography of a southern dunlin (Calidris alpina schinzii) breeding population. Using a stochastic renesting model that includes within‐season variation in breeding parameters, we evaluated the effect of grazing time and stocking rates on reproduction. The census data indicated that the population was stable when nest trampling was prevented, but detailed demographic models showed that the population on managed meadows was a sink that persisted by attracting immigrants. Even small reductions in reproductive success caused by trampling were detrimental to long‐term viability. We suggest that the best management strategy is to postpone grazing to after the 19th of June, which is about three weeks later than what is optimal from the farmer's point of view. The differing results from the two evaluation approaches warn against planning and evaluating management only based on census population size and highlight the need to consider target‐specific life history characteristics and demography. Even though grazing management is crucial for creating and maintaining suitable habitats, we found that it was insufficient in maintaining a viable population without additional measures that increase nest success. In the presently studied case and in populations with similar breeding cycles, impacts from nest trampling can be avoided by starting grazing when about 70% of the breeding season has past.     

Furrow Constriction in Animal Cell Cytokinesis

Cytokinesis is the process of physical cleavage at the end of cell division; it proceeds by ingression of an acto-myosin furrow at the equator of the cell. Its failure leads to multinucleated cells and is a possible cause of tumorigenesis. Here, we calculate the full dynamics of furrow ingression and predict cytokinesis completion above a well-defined threshold of equatorial contractility. The cortical acto-myosin is identified as the main source of mechanical dissipation and active forces. Thereupon, we propose a viscous active nonlinear membrane theory of the cortex that explicitly includes actin turnover and where the active RhoA signal leads to an equatorial band of myosin overactivity. The resulting cortex deformation is calculated numerically, and reproduces well the features of cytokinesis such as cell shape and cortical flows toward the equator. Our theory gives a physical explanation of the independence of cytokinesis duration on cell size in embryos. It also predicts a critical role of turnover on the rate and success of furrow constriction. Scaling arguments allow for a simple interpretation of the numerical results and unveil the key mechanism that generates the threshold for cytokinesis completion: cytoplasmic incompressibility results in a competition between the furrow line tension and the cell poles’ surface tension.     

The Orientation and Dynamics of Estradiol and Estradiol Oleate in Lipid Membranes and HDL Disc Models

Estradiol (E₂) and E₂ oleate associate with high-density lipoproteins (HDLs). Their orientation in HDLs is unknown. We studied the orientation of E₂ and E₂ oleate in membranes and reconstituted HDLs, finding that E₂ and E₂ oleate are membrane-associated and highly mobile. Our combination of NMR measurements, molecular dynamics simulation, and analytic theory identifies three major conformations where the long axis of E₂ assumes a parallel, perpendicular, or antiparallel orientation relative to the membrane’s z-direction. The perpendicular orientation is preferred, and furthermore, in this orientation, E₂ strongly favors a particular roll angle, facing the membrane with carbons 6, 7, 15, and 16, whereas carbons 1, 2, 11, and 12 point toward the aqueous phase. In contrast, the long axis of E₂ oleate is almost exclusively oriented at an angle of ∼60° to the z-direction. In such an orientation, the oleoyl chain is firmly inserted into the membrane. Thus, both E₂ and E₂ oleate have a preference for interface localization in the membrane. These orientations were also found in HDL discs, suggesting that only lipid-E₂ interactions determine the localization of the molecule. The structural mapping of E₂ and E₂ oleate may provide a design platform for specific E₂-HDL-targeted pharmacological therapies.     

Phospholipid Transfer Protein Is Expressed in Cerebrovascular Endothelial Cells and Involved in High Density Lipoprotein Biogenesis and Remodeling at the Blood-Brain Barrier

Phospholipid transfer protein (PLTP) is a key protein involved in biogenesis and remodeling of plasma HDL. Several neuroprotective properties have been ascribed to HDL. We reported earlier that liver X receptor (LXR) activation promotes cellular cholesterol efflux and formation of HDL-like particles in an established in vitro model of the blood-brain barrier (BBB) consisting of primary porcine brain capillary endothelial cells (pBCEC). Here, we report PLTP synthesis, regulation, and its key role in HDL metabolism at the BBB. We demonstrate that PLTP is highly expressed and secreted by pBCEC. In a polarized in vitro model mimicking the BBB, pBCEC secreted phospholipid-transfer active PLTP preferentially to the basolateral (“brain parenchymal”) compartment. PLTP expression levels and phospholipid transfer activity were enhanced (up to 2.5-fold) by LXR activation using 24(S)-hydroxycholesterol (a cerebral cholesterol metabolite) or TO901317 (a synthetic LXR agonist). TO901317 administration elevated PLTP activity in BCEC from C57/BL6 mice. Preincubation of HDL₃ with human plasma-derived active PLTP resulted in the formation of smaller and larger HDL particles and enhanced the capacity of the generated HDL particles to remove cholesterol from pBCEC by up to 3-fold. Pre-β-HDL, detected by two-dimensional crossed immunoelectrophoresis, was generated from HDL₃ in pBCEC-derived supernatants, and their generation was markedly enhanced (1.9-fold) upon LXR activation. Furthermore, RNA interference-mediated PLTP silencing (up to 75%) reduced both apoA-I-dependent (67%) and HDL₃-dependent (30%) cholesterol efflux from pBCEC. Based on these findings, we propose that PLTP is actively involved in lipid transfer, cholesterol efflux, HDL genesis, and remodeling at the BBB.     

TgaA,a VirB1-Like Component Belonging to a Putative Type IV Secretion System of Bifidobacterium bifidum MIMBb75

Bifidobacterium bifidum MIMBb75 is a human intestinal isolate demonstrated to be interactive with the host and efficacious as a probiotic. However, the molecular biology of this microorganism is yet largely unknown. For this reason, we undertook whole-genome sequencing of B. bifidum MIMBb75 to identify potential genetic factors that would explain the metabolic and probiotic attributes of this bacterium. Comparative genomic analysis revealed a 45-kb chromosomal region that comprises 19 putative genes coding for a potential type IV secretion system (T4SS). Thus, we undertook the initial characterization of this genetic region by studying the putative virB1-like gene, named tgaA. Gene tgaA encodes a peptidoglycan lytic enzyme containing two active domains: lytic murein transglycosylase (LT, cd00254.3) and cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP, pfam05257.4). By means of several in vitro assays, we experimentally confirmed that protein TgaA, consistent with its computationally assigned role, has peptidoglycan lytic activity, which is principally associated to the LT domain. Furthermore, immunofluorescence and immunogold labeling showed that the protein TgaA is abundantly expressed on the cell surface of B. bifidum MIMBb75. According to the literature, the T4SSs, which have not been characterized before in bifidobacteria, can have important implications for bacterial cell-to-cell communication as well as cross talk with host cells, justifying the interest for further studies aimed at the investigation of this genetic region.     

Population‐level consequences of risky dispersal

Achieving sufficient connectivity between populations is essential for persistence, but costs of dispersal may select against individual traits or behaviours that, if present, would improve connectivity. Existing dispersal models tend to ignore the multitude of risks to individuals: while many assess the effect of mortality costs, there is also a risk of failing to find new habitat, especially when the entire inhabitable area remains both small and fragmented. There are few known rules governing whether individuals evolve to disperse more, or less, than what is ideal for population connectivity and persistence. Here we aim to fill this gap, while also noting that evolution might not only produce suboptimal dispersal behaviour: it also influences individual heterogeneity in dispersal. Intuitively, we might expect heterogeneity to improve connectivity, as some individuals will travel far. However, we show that this is only true if dispersal distances on average are quite short; heterogeneity can also lead to reduced connectivity because it can reduce the proportion of the most profitable (‘safest’) intermediate dispersal distances. In general, our results show that conditions typically associated with conservation concerns (small and fragmented habitats inhabited by a species with a low birth rate) are also ones that are most likely to lead to suboptimal dispersal traits. This prompts the question of assisted dispersal in cases of urgent conservation concern.     

Use of CFSE staining of borreliae in studies on the interaction between borreliae and human neutrophils

Background  

Species of the tick-transmitted spirochete group Borrelia burgdorferi sensu lato (B. burgdorferi) cause Lyme borreliosis. Acute borrelial infection of the skin has unusual characteristics with only a mild local inflammatory response suggesting that the interaction between borreliae and the cells of the first-line defence might differ from that of other bacteria. It has been reported that human neutrophils phagocytose motile borreliae through an unconventional mechanism (tube phagocytosis) which is not observed with non-motile borreliae. Therefore, it would be of great interest to visualise the bacteria by a method not affecting motility and viability of borreliae to be able to study their interaction with the cells of the innate immunity. Carboxyfluorescein diacetate, succinimidyl ester (CFSE) labelling has been previously used for studying the adhesion of labelled bacteria to host cells and the uptake of labelled substrates by various cells using flow cytometry.     

Persistent joint swelling and Borrelia-specific antibodies in Borrelia garinii-infected mice after eradication of vegetative spirochetes with antibiotic treatment

We wanted to study the pathogenesis and the long-term manifestations of Borrelia garinii infection in SJL and C3H/He mice. We report here that B. garinii A218 causes a persisting infection in these mouse strains. Mice infected with intracutaneous inoculation of B. garinii at 4-5 weeks of age developed a disseminated infection and joint swelling within 2 weeks of inoculation and remained infected with joint symptoms until the end of follow-ups of up to 52 weeks. Treatment with ceftriaxone or ampicillin at 18 or 44 weeks of infection did not affect the joint swelling during the follow-ups of 19 and 8 weeks, respectively. However, B. garinii could not be cultured from any of the post mortem tissue samples of the treated mice, whereas the spirochete grew from samples of all untreated infected animals. Borrelia-specific IgG antibodies were detectable after 2 weeks of infection, and in late infection, all mice had high anti-borrelia IgG levels. Antibiotic treatment had no effect on antibody levels. Histology showed only slight changes in the joints of the infected mice with occasional lymphocyte infiltration, synovial proliferation and slight involvement of the Achilles' tendon. No difference was seen in the findings between ceftriaxone-treated and untreated mice. The results suggest that the presence of vegetative spirochetes is no prerequisite for persisting joint symptoms and elevated anti-borrelia IgG levels in these B. garinii-infected mice.     

Effects of neck muscle training in women with chronic neck pain: one-year follow-up study

Exercises are commonly recommended for chronic neck pain, but evidence-based guidelines do not explain what types of exercise. The aim of this randomized study was to evaluate the rate of change in neck strength following high- and low-intensity neck muscle training and their effects on pain and disability. One hundred eighty women with chronic neck pain were randomized into a high-intensity strength training group (STG), local muscle endurance training group (ETG), or control group (CG). The neck training consisted of isometric exercises in the STG and dynamic exercises in the ETG. Both groups performed dynamic exercises for the upper extremities. Strength tests, neck pain, and disability indices were evaluated at the baseline, at the follow-ups after 2 and 6 months in the training groups, and after 12 months in all groups. In both groups the greatest gains in neck strength, as well as decrease in neck pain and disability, were achieved during the first 2 months. However, the improvements continued up to 12 months. The STG achieved the greatest strength gains at all follow-ups. The CG showed only minor changes, and significant differences were found in favor of the training groups in all measures. The change in neck pain and disability indices correlated with the isometric neck strength (r = -0.22 [-0.36 to - 0.08] to -0.36 [-0.49 to -0.23]). Neck and shoulder muscle training was shown to be an effective therapy for chronic neck pain, resulting in early improvement in both the strength tests and subjective measures. The results can be maintained and even improved with long-term training.