Hepatic ACAT2 Knock Down Increases ABCA1 and Modifies HDL Metabolism in Mice

Objectives

ACAT2 is the exclusive cholesterol-esterifying enzyme in hepatocytes and enterocytes. Hepatic ABCA1 transfers unesterified cholesterol (UC) to apoAI, thus generating HDL. By changing the hepatic UC pool available for ABCA1, ACAT2 may affect HDL metabolism. The aim of this study was to reveal whether hepatic ACAT2 influences HDL metabolism.

Design

WT and LXRα/β double knockout (DOKO) mice were fed a western-type diet for 8 weeks. Animals were i.p. injected with an antisense oligonucleotide targeted to hepatic ACAT2 (ASO6), or with an ASO control. Injections started 4 weeks after, or concomitantly with, the beginning of the diet.

Results

ASO6 reduced liver cholesteryl esters, while not inducing UC accumulation. ASO6 increased hepatic ABCA1 protein independently of the diet conditions. ASO6 affected HDL lipids (increased UC) only in DOKO, while it increased apoE-containing HDL in both genotypes. In WT mice ASO6 led to the appearance of large HDL enriched in apoAI and apoE.

Conclusions

The use of ASO6 revealed a new pathway by which the liver may contribute to HDL metabolism in mice. ACAT2 seems to be a hepatic player affecting the cholesterol fluxes fated to VLDL or to HDL, the latter via up-regulation of ABCA1.     

Multidimensional Human Dynamics in Mobile Phone Communications

In today''s technology-assisted society, social interactions may be expressed through a variety of techno-communication channels, including online social networks, email and mobile phones (calls, text messages). Consequently, a clear grasp of human behavior through the diverse communication media is considered a key factor in understanding the formation of the today''s information society. So far, all previous research on user communication behavior has focused on a sole communication activity. In this paper we move forward another step on this research path by performing a multidimensional study of human sociality as an expression of the use of mobile phones. The paper focuses on user temporal communication behavior in the interplay between the two complementary communication media, text messages and phone calls, that represent the bi-dimensional scenario of analysis. Our study provides a theoretical framework for analyzing multidimensional bursts as the most general burst category, that includes one-dimensional bursts as the simplest case, and offers empirical evidence of their nature by following the combined phone call/text message communication patterns of approximately one million people over three-month period. This quantitative approach enables the design of a generative model rooted in the three most significant features of the multidimensional burst - the number of dimensions, prevalence and interleaving degree - able to reproduce the main media usage attitude. The other findings of the paper include a novel multidimensional burst detection algorithm and an insight analysis of the human media selection process.     

Spontaneous Group Synchronization of Movements and Respiratory Rhythms

We tested whether pre-assigned arm movements performed in a group setting spontaneously synchronized and whether synchronization extended to heart and respiratory rhythms. We monitored arm movements, respiration and electrocardiogram at rest and during spontaneous, music and metronome-associated arm-swinging. No directions were given on whether or how the arm swinging were to be synchronized between participants or with the external cues. Synchronization within 3 groups of 10 participants studied collectively was compared with pseudo-synchronization of 3 groups of 10 participants that underwent an identical protocol but in an individual setting. Motor synchronization was found to be higher in the collective groups than in the individuals for the metronome-associated condition. On a repetition of the protocol on the following day, motor synchronization in the collective groups extended to the spontaneous, un-cued condition. Breathing was also more synchronized in the collective groups than in the individuals, particularly at rest and in the music-associated condition. Group synchronization occurs without explicit instructions, and involves both movements and respiratory control rhythms.     

Setae from Larvae of the Northern Processionary Moth (Thaumetopoea pinivora,TP) Stimulate Proliferation of Human Blood Lymphocytes In Vitro

Larvae of the Northern pine processionary moth (Thaumetopoea pinivora, TP) carry microscopic needles (setae), which by penetrating skin and mucous membranes, may cause inflammatory/immune derived symptoms in man. In the present study the stimulatory effects of setae on human blood lymphocytes in vitro was investigated. Blood mononuclear cells were separated from venous blood or buffy coat of ten healthy individuals, six previously exposed to setae and four with no known exposure. Lymphoproliferation was measured as uptake of ³H-thymidine. Setae were prepared from TP larvae. Setae and saline setae extracts stimulated proliferation of T-lymphocytes in the presence of monocytic cells. Stimulation was pronounced in cells from persons who had been exposed to setae, and weak in cells from non-exposed donors. Chitin also induced lymphocyte proliferation in most donors, but to a lesser extent and independently of donor''s previous exposure to setae. In conclusion, setae contain molecules that in the presence of monocytes activate human T-lymphocytes to proliferation. The antigenic nature of stimulatory molecules was supported by the significantly stronger lymphocyte response in persons previously exposed to setae than in non-exposed donors. The nature of such molecules remains to be defined.     

Helicobacter pylori Infection, Intestinal Metaplasia, and Gastric Cancer Risk in Eastern Siberia

Background: The incidence of gastric cancer (GC) is extremely high in Russia and eastern Siberia, where information on the epidemiology of Helicobacter pylori infection is fragmentary. Aims: To assess the prevalence of both H. pylori infection (including CagA status) and intestinal metaplasia (IM) in Russian and eastern Siberian populations carrying a different risk of GC. Materials and Methods: A sample of 2129 consecutive patients was considered, including 689 Europoids and 1440 Mongoloids (493 Evenks, 533 Khakass people, and 414 Tuvans), who all underwent serum sampling and upper gastrointestinal endoscopy. H. pylori status was established (ELISA, urease test, and histology), and IgG anti‐CagA antibodies were assessed (ELISA) in H. pylori‐positive cases. At least 3 biopsy samples per patient were considered, and IM was scored as present versus absent. The prevalence of H. pylori, CagA+ve status, and IM was compared with the incidence of GC according to the regional cancer registries. Results: The prevalence of H. pylori was similar for the Europoids and Mongoloids (93.6 vs 94.3%). The prevalence of CagA+ve infection was as follows: Europoids 61.2%, Evenks 36.4%, Khakass 44.0%, Tuvans 60.0% (p_1vs2 < .001; p_1vs3 < .001; p_2vs4 < .001; p_3vs4 < .001). The prevalence of IM was as follows: Europoids 10.7%, Evenks 5.1%, Khakass 9.8%, and Tuvans 23.4% (p_1vs2 = .001; p_1vs4 < .001; p_2vs4 < .001; p_3vs4 < .001). The incidence of GC (per 100,000 population/year) was as follows: Europoids 33.2; Evenks 18.2; Khakass 20.2; Tuvans 50.7 (p_1vs2 = 0.04; p_1vs3 = .05; p_2vs4 < .001; p_3vs4 < .001). Conclusion: H. pylori infection is consistently high in Russian and eastern Siberian populations; ethnicities with similar prevalence of CagA+ve status had different prevalence of IM and incidence of GC. As expected, IM prevalence correlated with the incidence of GC. Host‐related and/or environmental factors may explain discrepancies between H. pylori status, the prevalence of IM, and the incidence of GC.     

Early assessment of the impact of alien species: differential consequences of an invasive crayfish on adult and larval amphibians

Aim Early assessment of the impact of invasive alien species is crucial to set up timely management, but often the impact is evident when it is too late for action. We evaluated relationships between the alien crayfish, Procambarus clarkii, the distribution of native amphibians, and the abundance of their larvae. We assessed whether considering measures of reproductive success provide a more prompt measure of impact than considering just species distribution. Location One hundred and twenty‐five wetlands in Northern Italy, in an area recently invaded by P. clarkii. Methods We surveyed wetlands to assess the presence of breeding activity of amphibians and the distribution of P. clarkii. We measured the abundance of amphibian larvae before metamorphosis through pipe sampling. We built models analysing the relationships between amphibian and crayfish distribution, while taking into account spatial autocorrelation and environmental features. Analyses were performed at both the species level (generalized linear models and spatial eigenvector mapping) and community level (constrained redundancy analysis). Results In terms of breeding site distribution, only two amphibians (Lissotriton vulgaris and Hyla intermedia) were negatively associated with P. clarkii, while the relationships between other the species and P. clarkii were positive or not significant. However, larval abundance for all amphibian species was negatively associated with the alien crayfish. Analyses performed at community and single species levels yielded consistent results. Main conclusions Procambarus clarkii impacts amphibians through different processes. Newts probably avoid invaded wetlands for breeding. Other species attempt breeding in wetlands with crayfish, but suffer very low success. Considering distribution data alone would not provide a correct picture of the impact of this alien species; measures of reproductive success may allow a more accurate assessment of the impact.     

A comparative analysis of DNA methylation across human embryonic stem cell lines

Background  

We performed a comparative analysis of the genome-wide DNA methylation profiles from three human embryonic stem cell (HESC) lines. It had previously been shown that HESC lines had significantly higher non-CG methylation than differentiated cells, and we therefore asked whether these sites were conserved across cell lines.     

Prediction of amyloid aggregation in vivo

Many human diseases owe their pathology, to some degree, to the erroneous conversion of proteins from their soluble state into fibrillar, β-structured aggregates, often referred to as amyloid fibrils. Neurodegenerative diseases, such as Alzheimer and spongiform encephalopathies, as well as type 2 diabetes and both localized and systemic amyloidosis, are among the conditions that are associated with the formation of amyloid fibrils. Several mathematical tools can rationalize and even predict important parameters of amyloid fibril formation. It is not clear, however, whether such algorithms have predictive powers for in vivo systems, in which protein aggregation is affected by the presence of other biological factors. In this review, we briefly describe the existing algorithms and use them to predict the effects of mutations on the aggregation of specific proteins, for which in vivo experimental data are available. The comparison between the theoretical predictions and the experimental data obtained in vivo is shown for each algorithm and experimental data set, and statistically significant correlations are found in most cases.