Effects of altered thyroid state on the inhibition produced by locus coeruleus in purkinje cells in the rat

Summary The number of cerebellar Purkinje cells inhibited after locus coeruleus stimulation was found to be greater in hyperthyroid rats than in control healthy animals; these in turn showed a higher percentage of inhibited cells than hypothyroid rats. It is concluded that thyroid hormone is capable of modulating synaptic activity in the LC-PC pathway.     

ALCAM/CD166 adhesive function is regulated by the tetraspanin CD9

ALCAM/CD166 is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs) which mediates intercellular adhesion through either homophilic (ALCAM–ALCAM) or heterophilic (ALCAM–CD6) interactions. ALCAM-mediated adhesion is crucial in different physiological and pathological phenomena, with particular relevance in leukocyte extravasation, stabilization of the immunological synapse, T cell activation and proliferation and tumor growth and metastasis. Although the functional implications of ALCAM in these processes is well established, the mechanisms regulating its adhesive capacity remain obscure. Using confocal microscopy colocalization, and biochemical and functional analyses, we found that ALCAM directly associates with the tetraspanin CD9 on the leukocyte surface in protein complexes that also include the metalloproteinase ADAM17/TACE. The functional relevance of these interactions is evidenced by the CD9-induced upregulation of both homophilic and heterophilic ALCAM interactions, as reflected by increased ALCAM-mediated cell adhesion and T cell migration, activation and proliferation. The enhancement of ALCAM function induced by CD9 is mediated by a dual mechanism involving (1) augmented clustering of ALCAM molecules, and (2) upregulation of ALCAM surface expression due to inhibition of ADAM17 sheddase activity.     

Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer

Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.     

Cognitive? Science?

Cognitive Science is a promising field of research that deals with one of the most fundamental questions ever: how do beings know? However, despite the long and extensive tradition of the field it has not yet become an area of knowledge with scientific identity. This is primarily due to three reasons: the lack of boundaries in defining the object of study, i.e. cognition, the lack of a precise, robust and consistent scientific methodology and results, and the inner problems derived from its interdisciplinary nature. This paper presents a background review, a theoretical frame and a humble reflection on these topics in order to arouse the internal debate among readers once more.     

Effects of thyroid state on brain stem responses to iontophoretic noradrenaline

Summary Responses to iontophoretic NA were increased in hyperthyroid rats and decreased in hypothyroid animals. No effect was observed on acetylcholine and glycine responses tested in the same way.This work was aided by grants from Consejo de Desarrollo Cientifico y Humanistico U.C.V. and CONICIT proyecto 51.26.SI-086.     

The biology of interleukin-1: emerging concepts in the regulation of the actin cytoskeleton and cell junction dynamics

Interleukin (IL)-1 is a proinflammatory cytokine with important roles in innate immunity, as well as in normal tissue homeostasis. Interestingly, recent studies have also shown IL-1 to function in the dynamics of the actin cytoskeleton and cell junctions. For example, treatment of different epithelia with IL-1α often results in the restructuring of the actin network and cell junctions, thereby leading to junction disassembly. In this review, we highlight new and interesting findings that show IL-1 to be a critical player of restructuring events in the seminiferous epithelium of the testis during spermatogenesis.     

Functional interplay between tetraspanins and proteases

Several recent publications have described examples of physical and functional interations between tetraspanins and specific membrane proteases belonging to the TM-MMP and α-(ADAMs) and γ-secretases families. Collectively, these examples constitute an emerging body of evidence supporting the notion that tetraspanin-enriched microdomains (TEMs) represent functional platforms for the regulation of key cellular processes including the release of surface protein ectodomains ("shedding"), regulated intramembrane proteolysis ("RIPing") and matrix degradation and assembly. These cellular processes in turn play a crucial role in an array of physiological and pathological phenomena. Thus, TEMs may represent new therapeutical targets that may simultaneously affect the proteolytic activity of different enzymes and their substrates. Agonistic or antagonistic antibodies and blocking soluble peptides corresponding to tetraspanin functional regions may offer new opportunities in the treatment of pathologies such as chronic inflammation, cancer, or Alzheimer's disease. In this review article, we will discuss all these aspects of functional regulation of protease activities by tetraspanins.     

Action Research in Reverse Logistics for End-Of-Life Tire Recycling

At the end of their product life cycle, tires require special handling and treatment in order to avoid damaging the environment and society. Reverse Logistics (RL) is necessary to manage this type of solid waste. In Brazilian cities, collection is one of the bottlenecks. One of the main difficulties in this process is enabling joint-action between the main stakeholders: Final consumers, the government and private companies. The main objective of this paper is to identify e implement opportunities for improvement in the collection phase of end-of-life tires through action-research, involving simultaneous participation between public and private organizations. The motive for this is that the knowledge generated can serve as a basis of information and references which aid in decision-making for public authorities who need to start similar programs or improve existing ones. The Action-Research occurred in a Brazilian city with less than 100,000 inhabitants, which fits the profile of 94.91% of the country’s municipalities. Final results proved the efficiency of the action-research proposal; after implementing the changes, the monthly collections grew by 50% (action), and the Action-Research team was able to generate and document knowledge which can now help other cities to improve their own processes.     

A germline variant in the TP53 polyadenylation signal confers cancer susceptibility

To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).     

Genetic variation in natural populations: Morphological traits inDrosophila melanogaster

Summary In a wild population ofDrosophila melanogaster located near Madrid (Spain), it has been found that the frequency of morphological mutant phenotypes is 0.36 per captured female. The study of these females shows that they carry 3.6 recessive mutants in heterozygous condition per female. The genetic variability found is higher than the frequencies observed by other authors in other natural populations.I thank Dr F.J. Ayala for useful discussions and help in preparing the English text.