Initial characterization of the carbohydrate structure of MCP-1

MCP-1 is the principle monocyte chemoattractant produced by tumor cells in vitro. We previously identified different isoforms of MCP-1. Here we report that two predominant isoforms of MCP-1 (13 kD and 9 kD) can be distinguished by lectin binding. The results indicate that the disaccharide galactose-beta 1-3D-N-acetyl galactosamine is present on the 13 kD MCP-1 isoform but not the 9 kD isoform. Glycosylation of the 13 kD MCP-1 isoform does not appear to significantly change its antigenic properties and also does not affect its capacity to induce monocyte migration.     

Counseling Parents of Retarded Children

Recently pediatricians have become more interested in the retarded child and his family and have come to realize that they have been ill-prepared to face the many problems that continually arise. A basic understanding of the role of parents and their aspirations, coupled with a knowledge of interviewing, techniques will enable them to face these problems with greater assurance. In addition, a knowledge of the community facilities and resources is necessary. This will entail direct contact with schools, parent groups, state hospitals for the retarded as well as state and local agencies which deal with the retarded.     

Laboratory evolution of adenylyl cyclase independent learning in Drosophila and missing heritability

Gene interactions are acknowledged to be a likely source of missing heritability in large‐scale genetic studies of complex neurological phenotypes. However, involvement of rare variants, de novo mutations, genetic lesions that are not easily detected with commonly used methods and epigenetic factors also are possible explanations. We used a laboratory evolution study to investigate the modulatory effects of background genetic variation on the phenotypic effect size of a null mutation with known impact on olfactory learning. To accomplish this, we first established a population that contained variation at just 23 loci and used selection to evolve suppression of the learning defect seen with null mutations in the rutabaga adenylyl cyclase. We thus biased the system to favor relatively simplified outcomes by choosing a Mendelian trait and by restricting the genetic variation segregating in the population. This experimental design also assures that the causal effects are among the known 23 segregating loci. We observe a robust response to selection that requires the presence of the 23 variants. Analyses of the underlying genotypes showed that interactions between more than two loci are likely to be involved in explaining the selection response, with implications for the missing heritability problem.     

The Integrity of the TRP Domain Is Pivotal for Correct TRPV1 Channel Gating

Transient receptor potential vanilloid subtype I (TRPV1) is a thermosensory ion channel that is also gated by chemical substances such as vanilloids. Adjacent to the channel gate, this polymodal thermoTRP channel displays a TRP domain, referred to as AD1, that plays a role in subunit association and channel gating. Previous studies have shown that swapping the AD1 in TRPV1 with the cognate from the TRPV2 channel (AD2) reduces protein expression and produces a nonfunctional chimeric channel (TRPV1-AD2). Here, we used a stepwise, sequential, cumulative site-directed mutagenesis approach, based on rebuilding the AD1 domain in the TRPV1-AD2 chimera, to unveil the minimum number of amino acids needed to restore protein expression and polymodal channel activity. Unexpectedly, we found that virtually full restitution of the AD1 sequence is required to reinstate channel expression and responses to capsaicin, temperature, and voltage. This strategy identified E692, R701, and T704 in the TRP domain as important for TRPV1 activity. Even conservative mutagenesis at these sites (E692D/R701K/T704S) impaired channel expression and abolished TRPV1 activity. However, the sole mutation of these positions in the TRPV1-AD2 chimera (D692E/K701R/S704T) was not sufficient to rescue channel gating, implying that other residues in the TRP domain are necessary to endow activity to TRPV1-AD2. A biophysical analysis of a functional chimera suggested that mutations in the TRP domain raised the energetics of channel gating by altering the coupling of stimuli sensing and pore opening. These findings indicate that inter- and/or intrasubunit interactions in the TRP domain are essential for correct TRPV1 gating.     

Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: A possible role for SirT3 activation

Berberine is an isoquinoline alkaloid with anti-diabetic properties. Despite the central role of liver and thus hepatic mitochondria in whole-body metabolism, berberine effects on hepatic mitochondrial function in an obesity model are still unknown. Here, we demonstrate that berberine treatment recovers mitochondrial efficiency when altered by a high-fat feeding. Mitochondria isolated from the liver of high-fat fed rats exhibited decreased capacity to accumulate calcium and impaired oxidative phosphorylation (OXPHOS) capacity, as shown by impaired mitochondrial membrane potential, oxygen consumption and cellular ATP levels. Interestingly, the recovery of mitochondrial function by berberine was associated with an increased activity of the mitochondrial sirtuin 3 (SirT3). In conclusion, berberine potent protective effects against metabolic syndrome may rely on increasing mitochondrial SirT3 activity, normalizing mitochondrial function and preventing a state of energetic deficit caused by impaired OXPHOS.     

Percent composition of fatty acids in Tigriopus fulvus from rocky pools on the Ligurian coast (Copepoda harpacticoida)

The study concerns the Tigriopus fulvus specimens fatty acid composition, sampled in Ligurian coast rockpools from September 1980 to June 1981. By the study of frequency distribution it was observed that the fatty acid found in greater quantity was the palmitic one, followed by the palmitoleic, the oleic and stearic acids. Short and long chain fatty acids are less frequent. Investigation about each fatty acid concentration shows that the seasonal trends between males and females are different and the trend of some fatty acids (e.g. linolenic and stearic acid) is characteristic.     

Seroprevalence and Potential Risk Factors for Helicobacter pylori Infection in Brazilian Children

Background: Helicobacter pylori infection has been proved to be of great relevance to public health in unindustrialized countries, especially in low socioeconomic groups. Poor hygiene, deficient sanitation, and crowded conditions have been reported as risk factors for this infection. In this work, we investigated whether social and demographic characteristics were associated with anti‐H. pylori IgG antibodies in 1104 children aged 4–11 years old from Salvador, a large city located in northeastern Brazil. Methods: Standardized questionnaires were used to obtain social, demographic, and environmental data for the studied population in two periods of time (from 1997 to 2003 and in 2005). Anti‐H. pylori IgG antibodies were assessed by indirect enzyme‐linked immunosorbent assay in 2005. Results: Anti‐H. pylori IgG antibody was present in 28.7% of the children. Among the studied variables, the following were positively associated with the presence of anti‐H. pylori antibodies in multivariable analyses: age above 8 years old (OR = 1.72, 95% CI = 1.23–2.40), a larger sibling number (OR = 1.66, 95% CI = 1.26–2.18), nursery attendance (OR = 1.49, 95% CI = 1.04–2.12), location of the house at an unpaved street (OR = 2.03, 95% CI = 1.44–2.87) and absence of a flush toilet (OR = 1.32, 95% CI = 1.00–1.74). Conclusion: Our data show that H. pylori infection in children from a major Brazilian city is associated with variables indicative of a crowded environment and deficient sanitation/habitation conditions, leading to the conclusion that improvements in hygiene and social conditions may protect children against this infection.