Application of the disulfide trapping approach to explain the antiparallel assembly of dimeric rabbit uteroglobin: A preliminary study using short peptide models

The spontaneous air oxidation of the peptides H-GICPRFAHVIENLL- NH2 and Ac-LPQTTRENIMKLTEKIVKSPLCM-OH, whose sequences correspond to the helicoidal fragments 1–14 and 48–70 of the monomer of rabbit uteroglobin, was studied. While no oxidation products were observed in the absence of trifluoroethanol, the heterodimer was formed selectively in the presence of the structuring agent. Head-to-head and tail-to-tail homodimers were not detected under these conditions. These results suggest that the N- and C- terminal extremes of the monomer of uteroglobin might contain enough structural information to govern dimerization with a head-tail topology, through a selective helix-to-helix recognition process.     

Role of GM3-enriched microdomains in signal transduction regulation in T lymphocytes

Gangliosides, sialic acid containing glycosphigolipids, are ubiquitous constituents of cell plasma membranes. Each cell type shows a peculiar ganglioside expression pattern. In human T lymphocytes monosialoganglioside GM3 represents the main ganglioside constituent of cell plasma membrane where it is concentrated in glycosphingolipid-enriched microdomains (GEM). The presence of tyrosine kinase receptors, mono- (Ras, Rap) and heterotrimeric G proteins, Src-like tyrosine kinases (lck, lyn, fyn), PKC isozymes, glycosylphosphatidylinositol (GPI)-anchored proteins and, after T cell activation, the Syk-family kinase Zap-70, prompts these portions of the plasma membrane to be considered as “glycosignaling domains.” In particular, during T cell activation and/or other dynamic functions of the cell, such as apoptosis, key signaling molecules are recruited to these microdomains, where they strictly interact with GM3. The association of transducer proteins with GM3 in microdomains suggests that this ganglioside is the main marker of GEM in human lymphocytes and is a component of a cell plasma membrane multimolecular signaling complex involved in cell-cell interaction, signal transduction, and cell activation. Published in 2004. This revised version was published online in August 2006 with corrections to the Cover Date.     

Effects of hyper- and hypothyroidism on thyroid hormone concentrations in regions of the rat brain

The purpose of this study was to investigate the effects of hyper- and hypothyroidism on thyroid hormone concentrations and deiodinase activities in nine regions of the rat brain. Four weeks of treatment with 75 microg thyroxine (T4)/kg body wt induced a two- to threefold increase in T4 levels in all of these brain regions, whereas the 3,5,3'-triiodothyronine (T3) concentrations were reduced in five brain regions and remained unchanged in four. Even after 8 wk treatment with 300 microg T4/kg, the T3 concentrations remained normal in cortical areas, the hippocampus and amygdala, and were elevated only in areas in which inner-ring deiodinase activity was low or absent, and in the hypothalamus. At the subcellular level, nuclear concentrations of T3 were diminished in hypothyroidism but remained unaltered in hyperthyroidism in all areas except the hypothalamus, where they were enhanced. Cortical mitochondrial succinate dehydrogenase activity was reduced in both hypo- and hyperthyroidism in spite of normal T3 concentrations in hyperthyroid animals. The results show that nuclear T3 concentrations fall in hypothyroidism but do not change during severe hyperthyroidism in any brain region except the hypothalamus. Further research is thus needed to clarify the mechanisms mediating the numerous biochemical and psychological effects of hyperthyroidism.     

Protein biomarkers for in vitro testing of embryotoxicity

There are new challenges for hazard and risk assessment in the chemical industry with regard to REACH legislation in Europe and related activities in the U.S. and Japan, which require the development of novel in vitro models for the molecular characterization of drug- or chemical-related effects replacing conventional animal testing. In the frame of a European FP6 project on reproductive toxicology ( www.reprotect.eu ), we prepared protein samples from mouse embryonic stem cells differentiated into contracting cardiomyocytes according to the validated embryonic stem cell test (EST) protocol, which had been exposed to toxic substances selected by an expert committee from different in vivo categories of embryotoxicity. Lysates were used to carry out the following investigations: (i) identify optimal dose range conditions in the EST that are suitable for (ii) performing a differential quantitative proteomic study of underlying molecular pathways, (iii) define classes of substances with similar proteomic response patterns, (iv) relate these classes to the traditional in vivo categories of embryotoxicity with (v) the final goal to identify novel surrogate protein biomarker candidates for embryo toxicity. We found two distinct classes of toxic substances (Dinoseb, Ochratoxin-A, and Nitrofen vs β-aminoproprionitril, Metoclopramide, Doxylamine succinate, and d-penicillamine) with clear pathway-related differences in their proteomic patterns. Most notably, different responses to cluster 1 and cluster 2 substances were observed for Heat shock protein β-1, Ras-GTPase-activating protein SH3-domain binding protein, Ran binding protein 5, and Calreticulin, Dihydropyrimidinase-like 2 (Ulip2 protein). On the other hand, Heat shock protein 8 and Fscn1 protein were down-regulated by all compounds from both clusters.     

Small males of the fiddler crab Austruca perplexa court more in the off-peak breeding period when large males court less

Journal of Ethology - Many animals adjust their reproductive investment in line with their current competitive abilities. High-quality individuals may breed in the peak breeding period because they...     

Matrix metalloproteinase-7 disrupts dendritic spines in hippocampal neurons through NMDA receptor activation

Dendritic spines are protrusions from the dendritic shaft that host most excitatory synapses in the brain. Although they first emerge during neuronal maturation, dendritic spines remain plastic through adulthood, and recent advances in the molecular mechanisms governing spine morphology have shown them to be exquisitely sensitive to changes in the micro-environment. Among the many factors affecting spine morphology are components and regulators of the extracellular matrix (ECM). Modification of the ECM is critical to the repair of injuries throughout the body, including the CNS. Matrix metalloproteinase (MMP)-7/matrilysin is a key regulator of the ECM during pathogen infection, after nerve crush and in encephalitogenic disorders. We have investigated the effects of MMP-7 on dendritic spines in hippocampal neuron cultures and found that it induces the transformation of mature, short mushroom-shaped spines into long, thin filopodia reminiscent of immature spines. These changes were accompanied by a dramatic redistribution of F-actin from spine heads into thick, rope-like structures in the dendritic shaft. Strikingly, MMP-7 effects on dendritic spines were similar to those of NMDA treatment, and both could be blocked by channel-specific antagonists. These findings are the first direct evidence that MMPs can influence the morphology of mature dendritic spines, and hence synaptic stability.     

Medical and psychological parameters in overweight and obese persons seeking treatment

The aim of the study was to analyse psychological characteristics and medical parameters in obese and overweight to identify the possible psychosocial consequences of obesity that may occur along with the numerous medical problems associated with excess body weight. Analysis was made on 296 patients (103 males and 193 females, median age 50, range 16-81) divided in three groups, depending on their Body mass index (BMI). Group I included 41 patients with BMI ranging from 25 to 29.9, group II included 170 patients with BMI from 30 to 34.9, and group III 85 patients with BM > or =35. We compared medical (glucose, cholesterol, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure, body fat percentage) and psychological parameters (anxiety, depression, pros and cons of losing weight, self efficacy and four stages of change) in the patients included in the study. Univariate analysis has shown statistically significant difference among obese and overweight patients in goal weight, systolic and diastolic blood pressure, body fat percentage, glucose and cholesterol serum level. People with higher BMI (>30) found more advantages (pros) over disadvantages (cons) of weight loss but the level of anxiety and depression did not differ significantly among those 3 groups of patients. The results have shown that overweight and obese people have serious medical problems. They also differ in some psychological characteristics which have to be taken into consideration. Therefore, approach to these patients should be multidisciplinary, including dietary care, physical activity, psychological and medical care.