Responses of adipose tissue lipoprotein lipase to weight loss affect lipid levels and weight regain in women

This study determines whether changes in abdominal (ABD) and gluteal (GLT) adipose tissue lipoprotein lipase (LPL) activity in response to a 6-mo weight loss intervention, comprised of a hypocaloric diet and low-intensity walking, affect changes in body composition, fat distribution, lipid metabolism, and the magnitude of weight regain in 36 obese postmenopausal women. Average adipose tissue LPL activity did not change with an average 5.6-kg weight loss, but changes in LPL activity were inversely related to baseline LPL activity (ABD: r = -0.60, GLT: r = -0.48; P < 0.01). The loss of abdominal body fat and decreases in total and low-density lipoprotein cholesterol were greater in women whose adipose tissue LPL activity decreased with weight loss despite a similar loss of total body weight and fat mass. Moreover, weight regain after a 6-mo follow-up was less in women whose adipose tissue LPL activity decreased than in women whose LPL increased (ABD: 0.9 +/- 0.5 vs. 2.8 +/- 0.6 kg, P < 0.05; GLT: 0.2 +/- 0.5 vs. 2.8 +/- 0.5 kg, P < 0.01). These results suggest that a reduction in adipose tissue LPL activity with weight loss is associated with improvements in lipid metabolic risk factors with weight loss and with diminished weight regain in postmenopausal women.     

A quantitative study of chromosomal elasticity and its influence on chromosome movement

Summary Chromosome elasticity and movement have been studied in living cells in two distinct situations: early anaphase stretch due to opposed external forces, and drag stretch — an elongation due to frictional resistance or drag on a chromosome being pulled toward one pole. Drag stretch provides a simultaneous display of both friction and elasticity and shows that chromosomes in living cells are elastic up to approximately six-fold increases in length.Neither early anaphase stretch nor drag stretch produce detectable alterations in the velocity of chromosome movement. A simple mechanical model is described which permits interpretation of this result for drag stretch: no matter how extensive, drag stretch should produce no change in the force required to maintain a given velocity of movement and hence should not alter movement velocity. Early anaphase stretch is a very different proposition, and additional assumptions leading to a quantitative model are necessary for its interpretation. Nevertheless it is reasonably certain that the amount of stretch actually seen in these circumstances would influence chromosome movement if the applied force were not increased over that necessary in the absence of stretch. It is concluded that the mitotic forces are continually adjusted to produce a standard velocity of movement even when an unusual hindrance to movement exists. The implications of this are considered, particularly in regard to the stretching and rupture of dikinetochoric (dicentric) bridges in anaphase.The quantitative version of the mechanical model for elasticity and movement can be applied to the drag stretch data, and permits calculation of the ratio between frictional and elastic coefficients. The chief assumptions are that the elasticity is Hookian, and the frictional resistance Newtonian in character. The model has not been critically tested, but it is consonant with existing data.This investigation was supported in part by research grant number RG-8480 from the Division of General Medical Sciences, United States Public Health Service.     

Comparative Hazard Identification by a Single Dose Lung Exposure of Zinc Oxide and Silver Nanomaterials in Mice

Comparative hazard identification of nanomaterials (NMs) can aid in the prioritisation for further toxicity testing. Here, we assessed the acute lung, systemic and liver responses in C57BL/6N mice for three NMs to provide a hazard ranking. A silver (Ag), non-functionalised zinc oxide (ZnO) and a triethoxycaprylylsilane functionalised ZnO NM suspended in water with 2% mouse serum were examined 24 hours following a single intratracheal instillation (I.T.). An acute pulmonary inflammation was noted (marked by a polymorphonuclear neutrophil influx) with cell damage (LDH and total protein) in broncho-alveolar lavage fluid (BALF) after administration of both non-functionalised and functionalised ZnO. The latter also induced systemic inflammation measured as an increase in blood neutrophils and a decrease in blood lymphocytes. Exposure to Ag NM was not accompanied by pulmonary inflammation or cytotoxicity, or by systemic inflammation. A decrease in glutathione levels was demonstrated in the liver following exposure to high doses of all three nanomaterials irrespective of any noticeable inflammatory or cytotoxic effects in the lung. By applying benchmark dose (BMD) modeling statistics to compare potencies of the NMs, we rank functionalised ZnO ranked the highest based on the largest number of affected endpoints, as well as the strongest responses observed after 24 hours. The non-functionalised ZnO NM gave an almost similar response, whereas Ag NM did not cause an acute response at similar doses.     

Differentiation Among Rodentibacter Species Based on 16S–23S rRNA Internal Transcribed Spacer Analysis

The internal transcribed spacer (ITS) regions of Rodentibacter pneumotropicus, R. heylii, R. rarus, R. ratti, and R. heidelbergensis and of a Rodentibacter-related β-hemolytic Pasteurellaceae taxon isolated from laboratory rodents were studied for their feasibility to discriminate among these species. The 6 species analyzed showed species-specific ITS patterns that were shared by the type strains and clinical isolates and that allowed their identification. Nevertheless, differentiating between the ITS band patterns of R. pneumotropicus and R. ratti is visually challenging. In all species tested, sequence analysis of the ITS fragments revealed a larger ITS^ile+ala, which contained the genes for tRNA^Ile(GAU) and tRNA^Ala(UGC), and a smaller ITS^glu with the tRNA^Glu(UUC) gene. The ITS sequences varied among the 6 species evaluated, displaying identity levels ranging from 62% to 86% for ITS^ile+ala and 68% to 90% for ITS^glu. Overall, ITS amplification proved to be a reliable method to differentiate among these important Pasteurellaceae species of laboratory rodents. Moreover, the ITS sequence variations recorded here might facilitate the design of probes for specific identification of these species. The ability to diagnose these organisms to the species level could increase our understanding of their clinical significance.

The members of the Pasteurellaceae isolated from rodents are among the most prevalent bacterial agents from experimental animal facilities.¹⁸ Recently, [Pasteurella] pneumotropica and its closely related rodent Pasteurellaceae were reclassified into 8 distinct species and 2 genomospecies within the new genus Rodentibacter.¹ The uncertain taxonomic position of [P.] pneumotropica complex has hindered understanding of the epidemiology, pathogenesis, diagnosis, and control of infections caused by these microorganisms.⁸ Currently R. pneumotropicus and R. heylii are considered to have tropism mainly toward mice, whereas R. ratti and R. heidelbergensis are rather rat-specific.^8,17 Despite their relatedness, isolates of Rodentibacter spp. of rat origin infected only a few mice by contact and experimentally, whereas mouse isolates infected all rats, thus showing that the rat isolates are more species specific than the mice isolates.¹⁵ We recently documented that R. heylii naturally infects both rats and mice.⁷ In addition to the known Rodentibacter species, a Rodentibacter-related β-hemolytic taxon is apparently often present in laboratory mice.^6,12 The members of the former [P.] pneumotropica complex (now Rodentibacter spp.) are generally regarded as classic opportunistic pathogens of rodents. However, little is known about the pathogenicity of the individual bacterial species.⁸The new taxonomic separation of the previous [P.] pneumotropica complex into Rodentibacter species supports better diagnostic assays among this complex group of bacteria. Nevertheless, simple molecular techniques to differentiate these organisms are currently available only for R. pneumotropicus and R. heylii; 16S rRNA gene sequencing is the only alternative for the remaining Rodentibacter species.The internal transcribed spacer (ITS) region has been used as a target for PCR-based identification and typing of many closely related bacteria, including Pasteurellaceae.¹³ We previously used this method to differentiate among R. pneumotropicus, R. heylii, and R. rarus, which were known as [P.] pneumotropica biotypes Jawetz and Heyl and Bisgaard Taxon 17 at that time.⁴In this current investigation, we extended the analysis of the 16S–23S ITS of the rRNA operons to R. ratti, R. heidelbergensis, and the Rodentibacter-related β-hemolytic taxon and compared them with the ITS of R. pneumotropicus, R. heylii, and R. rarus, as a basis for identification and differentiation within this group of closely related bacterial species. The length and sequence polymorphisms of the ITS allowed differentiation among the 6 species. The ability to diagnose Rodentibacter taxa at the species level could improve our understanding of their clinical significance.     

Specialists in ancient trees are more affected by climate than generalists

Ancient trees are considered one of the most important habitats for biodiversity in Europe and North America. They support exceptional numbers of specialized species, including a range of rare and endangered wood‐living insects. In this study, we use a dataset of 105 sites spanning a climatic gradient along the oak range of Norway and Sweden to investigate the importance of temperature and precipitation on beetle species richness in ancient, hollow oak trees. We expected that increased summer temperature would positively influence all wood‐living beetle species whereas precipitation would be less important with a negligible or negative impact. Surprisingly, only oak‐specialist beetles with a northern distribution increased in species richness with temperature. Few specialist beetles and no generalist beetles responded to the rise of 4°C in summer as covered by our climatic gradient. The negative effect of precipitation affected more specialist species than did temperature, whereas the generalists remained unaffected. In summary, we suggest that increased summer temperature is likely to benefit a few specialist beetles within this dead wood community, but a larger number of specialists are likely to decline due to increased precipitation. In addition, generalist species will remain unaffected. To minimize adverse impacts of climate change on this important community, long‐term management plans for ancient trees are important.     

Intentional Weight Loss and All-Cause Mortality: A Meta-Analysis of Randomized Clinical Trials

Background

Obesity is associated with increased mortality, and weight loss trials show rapid improvement in many mortality risk factors. Yet, observational studies typically associate weight loss with higher mortality risk. The purpose of this meta-analysis of randomized controlled trials (RCTs) of weight loss was to clarify the effects of intentional weight loss on mortality.

Methods

2,484 abstracts were identified and reviewed in PUBMED, yielding 15 RCTs reporting (1) randomization to weight loss or non-weight loss arms, (2) duration of ≥18 months, and (3) deaths by intervention arm. Weight loss interventions were all lifestyle-based. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated for each trial. For trials reporting at least one death (n = 12), a summary estimate was calculated using the Mantel-Haenszel method. Sensitivity analysis using sparse data methods included remaining trials.

Results

Trials enrolled 17,186 participants (53% female, mean age at randomization = 52 years). Mean body mass indices ranged from 30–46 kg/m², follow-up times ranged from 18 months to 12.6 years (mean: 27 months), and average weight loss in reported trials was 5.5±4.0 kg. A total of 264 deaths were reported in weight loss groups and 310 in non-weight loss groups. The weight loss groups experienced a 15% lower all-cause mortality risk (RR = 0.85; 95% CI: 0.73–1.00). There was no evidence for heterogeneity of effect (Cochran’s Q = 5.59 (11 d.f.; p = 0.90); I² = 0). Results were similar in trials with a mean age at randomization ≥55 years (RR = 0.84; 95% CI 0.71–0.99) and a follow-up time of ≥4 years (RR = 0.85; 95% CI 0.72–1.00).

Conclusions

In obese adults, intentional weight loss may be associated with approximately a 15% reduction in all-cause mortality.     

SveDem,the Swedish Dementia Registry – A Tool for Improving the Quality of Diagnostics,Treatment and Care of Dementia Patients in Clinical Practice

BackgroundThe Swedish Dementia Registry (SveDem) was developed with the aim to improve the quality of diagnostic work-up, treatment and care of patients with dementia disorders in Sweden.MethodsSveDem is an internet based quality registry where several indicators can be followed over time. It includes information about the diagnostic work-up, medical treatment and community support (www.svedem.se). The patients are diagnosed and followed-up yearly in specialist units, primary care centres or in nursing homes.ResultsThe database was initiated in May 2007 and covers almost all of Sweden. There were 28 722 patients registered with a mean age of 79.3 years during 2007–2012. Each participating unit obtains continuous online statistics from its own registrations and they can be compared with regional and national data. A report from SveDem is published yearly to inform medical and care professionals as well as political and administrative decision-makers about the current quality of diagnostics, treatment and care of patients with dementia disorders in Sweden.ConclusionSveDem provides knowledge about current dementia care in Sweden and serves as a framework for ensuring the quality of diagnostics, treatment and care across the country. It also reflects changes in quality dementia care over time. Data from SveDem can be used to further develop the national guidelines for dementia and to generate new research hypotheses.     

The RNA helicase DDX6 regulates cell-fate specification in neural stem cells via miRNAs

In neural stem cells (NSCs), the balance between stem cell maintenance and neuronal differentiation depends on cell-fate determinants such as TRIM32. Previously, we have shown that TRIM32 associates with the RNA-induced silencing complex and increases the activity of microRNAs such as Let-7a. However, the exact mechanism of microRNA regulation by TRIM32 during neuronal differentiation has yet to be elucidated. Here, we used a mass spectrometry approach to identify novel protein–protein interaction partners of TRIM32 during neuronal differentiation. We found that TRIM32 associates with proteins involved in neurogenesis and RNA-related processes, such as the RNA helicase DDX6, which has been implicated in microRNA regulation. We demonstrate, that DDX6 colocalizes with TRIM32 in NSCs and neurons and that it increases the activity of Let-7a. Furthermore, we provide evidence that DDX6 is necessary and sufficient for neuronal differentiation and that it functions in cooperation with TRIM32.