Organization and possible origin of the Bari-1 cluster in the heterochromatic h39 region of Drosophila melanogaster

The molecular organization of the heterochromatic h39 region of the Drosophila melanogaster second chromosome has been investigated by studying two BAC clones identified both by Southern blotting and by FISH experiments as containing tandem arrays of Bari1, a transposable element present only in this region. Such BAC clones appear to contain different portions of the h39 region since they differ in the DNA sequences flanking the Bari1 repeats on both sides. Thus, the 80 Bari1 copies estimated to be present in the h39 region are split into at least two separated subregions. On the basis of the analysis of the flanking sequences a possible mechanism depending on an aberrant activity of the Bari1 transposase is proposed for the genesis of the heterochromatic tandem arrays of the element.     

Oscillations in the prefrontal cortex: a gateway to memory and attention

We consider the potential role of oscillations in the prefrontal cortex (PFC) in mediating attention, working memory and memory consolidation. Activity in the theta, beta, and gamma bands is related to communication between PFC and different brain areas. While gamma/beta oscillations mediate bottom-up and top-down interactions between PFC and visual cortices, related to attention, theta rhythms are engaged by hippocampal/PFC interplay. These interactions are dynamic, depending on the nature and relevance of the information currently being processed. The profound modifications of the PFC neuronal network associated with changes in oscillatory coherence are controlled by neuromodulators such as dopamine, which thereby allow or prevent the formation of cell assemblies for information encoding and storage.     

A stapled chromogranin A-derived peptide homes in on tumors that express αvβ6 or αvβ8 integrins

Rationale: The αvβ6- and αvβ8-integrins, two cell-adhesion receptors upregulated in many tumors and involved in the activation of the latency associated peptide (LAP)/TGFβ complex, represent potential targets for tumor imaging and therapy. We investigated the tumor-homing properties of a chromogranin A-derived peptide containing an RGDL motif followed by a chemically stapled alpha-helix (called “5a”), which selectively recognizes the LAP/TGFβ complex-binding site of αvβ6 and αvβ8.Methods: Peptide 5a was labeled with IRDye 800CW (a near-infrared fluorescent dye) or with ¹⁸F-NOTA (a label for positron emission tomography (PET)); the integrin-binding properties of free peptide and conjugates were then investigated using purified αvβ6/αvβ8 integrins and various αvβ6/αvβ8 single - or double-positive cancer cells; tumor-homing, biodistribution and imaging properties of the conjugates were investigated in subcutaneous and orthotopic αvβ6-positive carcinomas of the pancreas, and in mice bearing subcutaneous αvβ8-positive prostate tumors.Results: In vitro studies showed that 5a can bind both integrins with high affinity and inhibits cell-mediated TGFβ activation. The 5a-IRDye and 5a-NOTA conjugates could bind purified αvβ6/αvβ8 integrins with no loss of affinity compared to free peptide, and selectively recognized various αvβ6/αvβ8 single- or double-positive cancer cells, including cells from pancreatic carcinoma, melanoma, oral mucosa, bladder and prostate cancer. In vivo static and dynamic optical near-infrared and PET/CT imaging and biodistribution studies, performed in mice with subcutaneous and orthotopic αvβ6-positive carcinomas of the pancreas, showed high target-specific uptake of fluorescence- and radio-labeled peptide by tumors and low non-specific uptake in other organs and tissues, except for excretory organs. Significant target-specific uptake of fluorescence-labeled peptide was also observed in mice bearing αvβ8-positive prostate tumors.Conclusions: The results indicate that 5a can home to αvβ6- and/or αvβ8-positive tumors, suggesting that this peptide can be exploited as a ligand for delivering imaging or anticancer agents to αvβ6/αvβ8 single- or double-positive tumors, or as a tumor-homing inhibitor of these TGFβ activators.     

Construct validity of the Short Form-36 Health Survey and its relationship with BMI in obese outpatients

Objective: To investigate the construct validity of the Short Form‐36 (SF‐36) Health Survey questionnaire in obese patients. Research Methods and Procedures: Our series consisted of 1735 obese patients (age, 44.7 ± 11.0 years; 1346 women) consecutively enrolled in the QUOVADIS study, an observational multicenter study of obese treatment‐seeking outpatients. The construct validity of the SF‐36 was assessed by main component analysis. Age‐, gender‐, and education‐adjusted general linear models were used to investigate the relationship between BMI and SF‐36 domains or factors identified by main component analysis. Results: BMI was significantly associated with poor health‐related quality of life in all eight SF‐36 domains, and the strongest association was observed with physical activity. Main components analysis generated a six‐factor solution explaining 59% of the observed variance. BMI was strongly associated with factors based on the loading of items regarding the physical activity domain and factors based on role‐physical and role‐emotional items or general health and bodily pain items. In contrast, mental health‐, vitality‐, and social functioning‐based factors were not related to BMI. Discussion: In obese treatment‐seeking outpatients, the clustering of SF‐36 items in main components is not significantly different from the domain‐based approach generally used, thus confirming the robustness of such a generic questionnaire in this specific condition. However, the peculiar clustering of some SF‐36 items and their relationship with BMI suggest that the health‐related quality of life profile of subjects belonging to that population may be better described with alternative aggregations of the SF‐36 items or with disease‐tailored questionnaires.     

Rheology of hydroxyethyl guar gum derivatives

The rheological properties of aqueous solutions of hydroxyethyl guar gum, a synthetic derivative of guar gum, have been studied under continuous and oscillatory shear flow conditions. Data obtained from both experimental techniques were satisfactorily fitted according to Cross-type models. The effect of polymer concentration, molecular weight and temperature on the rheological behavior of hydroxyethyl guar gum systems have been investigated and discussed in terms of rheological parameters like the zero-shear viscosity η₀ and the characteristic times λ and λ′.