Nestin is a neuroepithelial target gene of thyroid transcription factor-1, a homeoprotein required for forebrain organogenesis.

Thyroid transcription factor-1 (TTF-1, also known as NKX2.1 and T/EBP), a transcription factor belonging to the NKX-2 family of homeodomain-containing genes, plays an essential role in the organogenesis of the thyroid gland, lung, and ventral forebrain. Nestin is an intermediate filament protein strongly expressed in multipotential neuroepithelial stem cells and rapidly down-regulated during postnatal life. Here we show that stable fibroblastic clones expressing TTF-1 acquire a phenotype reminiscent of neuroepithelial cells in culture and up-regulate the endogenous nestin gene. TTF-1 transactivates in HeLa and NIH3T3 cells a reporter gene driven by a central nervous system-specific enhancer element from the second intron of the rat nestin gene, where it recognizes a DNA-binding site (NestBS) whose sequence resembles a nuclear hormone/cAMP-responsive element very different from canonical TTF-1 binding sites. Nuclear extracts from the head of mouse embryos form a retarded complex with NestBS of the same mobility of the extracts obtained from TTF1-expressing clones, which is either abolished or supershifted in the presence of two different antibodies recognizing the TTF-1 protein. Thus, the neuroepithelial marker nestin is a direct central nervous system-specific target gene of TTF-1, leading to the hypothesis that it might be the effector through which TTF-1 plays its role in the organogenesis of the forebrain

Musculocutaneous nerve variations. Meta-analysis of proportions and proposal for categorization

The musculocutaneous nerve (MCN) is one of the main terminal branches of the brachial plexus. It provides motor innervation to coracobrachialis, biceps brachii and brachialis muscles and sensory innervation to the skin of lateral side of the forearm. In the normal anatomical description, the MCN arises from lateral cord and don’t have communication with other terminal branches of brachial plexus. All motor branches arises from MCN, directly.[1] Despite these considerations, several variations of MCN have been reported. The most common are anomalous communications between MCN and median nerve. These communications could be relevant in clinical practice and could have several practical considerations that should be evaluated in different medical area, such as orthopedic surgery, traumatology or neurophysiology. Several classifications have been proposed but none of these is able to cover all aspects of this variation. Therefore, the aim of the present study are a systematic review of the available literature about MCN variations and a meta-analytic approach to define their prevalence.[2] At the same time, a new model of categorization with practical effects on clinical reasoning has been proposed. Several electronic databases have been searched. Articles have been screened and papers with anatomical description of MCN variations have been included. 43 out of 661 articles fulfilled inclusion criteria, with a description of 4695 brachial plexuses dissections. The random pooled prevalence of MCN variations is 18% (95%CI: 15-21%). The new categorization proposal is based on a 3 areas model: Area 1 (1A: absence of musculocutaneous nerve, 1B: variations before the division of the musculocutaneous nerve from lateral cord); Area 2: variations between origin of MCN from lateral cord and point of in coracobrachialis muscle (or same level if MCN does not pierce the muscle); Area 3: variations distal to point of entry in coracobrachialis muscle; Mixed areas: variations reported in more than a single area described above. Applying this model, the random pooled prevalence of reported variations is: Area 1A: 19% (95%CI: 11-28%), Area 1B: 26% (95%CI: 14-39%), Area 2: 46% (95%CI: 33- 59%), Area 3: 55% (95%CI: 40-70%), Mixed areas: 16 (95%CI: 8-25%). Therefore, MCN variations have a high prevalence. Among them, the most frequent are localized distal to coracobrachialis muscle. These results could be useful in clinical practice to point the attention at this anatomical region where variations in MCN are very common

Novel Polydiacetylene-Functionalized Nanostructures for Sensing Applications

n/

Ultrafast spectroscopy on water-processable PCBM: rod-coil block copolymer nanoparticles.

Using ultrafast spectroscopy, we investigate the photophysics of water-processable nanoparticles composed of a block copolymer electron donor and a fullerene derivative electron acceptor

Protein Isoaspartate Methyltransferase Prevents Apoptosis Induced by Oxidative Stress in Endothelial Cells: Role of Bcl-Xl Deamidation and Methylation

BACKGROUND:Natural proteins undergo in vivo spontaneous post-biosynthetic deamidation of specific asparagine residues with isoaspartyl formation. Deamidated-isomerized molecules are both structurally and functionally altered. The enzyme isoaspartyl protein carboxyl-O-methyltransferase (PCMT; EC 2.1.1.77) has peculiar substrate specificity towards these deamidated proteins. It catalyzes methyl esterification of the free alpha-carboxyl group at the isoaspartyl site, thus initiating the repair of these abnormal proteins through the conversion of the isopeptide bond into a normal alpha-peptide bond. Deamidation occurs slowly during cellular and molecular aging, being accelerated by physical-chemical stresses brought to the living cells. Previous evidence supports a role of protein deamidation in the acquisition of susceptibility to apoptosis. Aim of this work was to shed a light on the role of PCMT in apoptosis clarifying the relevant mechanism(s). METHODOLOGY/PRINCIPAL FINDINGS:Endothelial cells transiently transfected with various constructs of PCMT, i.e. overexpressing wild type PCMT or negative dominants, were used to investigate the role of protein methylation during apoptosis induced by oxidative stress (H(2)O(2); 0.1-0.5 mM range). Results show that A) Cells overexpressing "wild type" human PCMT were resistant to apoptosis, whereas overexpression of antisense PCMT induces high sensitivity to apoptosis even at low H(2)O(2) concentrations. B) PCMT protective effect is specifically due to its methyltransferase activity rather than to any other non-enzymatic interactions. In fact negative dominants, overexpressing PCMT mutants devoid of catalytic activity do not prevent apoptosis. C) Cells transfected with antisense PCMT, or overexpressing a PCMT mutant, accumulate isoaspartyl-containing damaged proteins upon H(2)O(2) treatment. Proteomics allowed the identification of proteins, which are both PCMT substrates and apoptosis effectors, whose deamidation occurs under oxidative stress conditions leading to programmed cell death. These proteins, including Hsp70, Hsp90, actin, and Bcl-xL, are recognized and methylated by PCMT, according to the general repair mechanism of this methyltransferase. CONCLUSION/SIGNIFICANCE:Apoptosis can be modulated by "on/off" switch partitioning the amount of specific protein effectors, which are either in their active (native) or inactive (deamidated) molecular forms. Deamidated proteins can also be functionally restored through methylation. Bcl-xL provides a case for the role of PCMT in the maintenance of functional stability of this antiapoptotic protein

Special Issue: Innovations in Semiconducting Block Copolymers

The current Special Issue entitled “Innovations in Semiconducting Block Copolymers” aims to discuss cutting-edge research regarding the synthesis, characterization and application of semiconducting block copolymers, with a special focus on the realization of novel and innovative nanostructured materials for the production of advanced devices suitable in different fields, ranging from sensors applications to optic photovoltaics [...

Chitosan-stabilized noble metal nanoparticles: study of their shape evolution and post-functionalization properties

none4nononeMassimo Ottonelli, Stefania Zappia, Anna Demartini, Marina AlloisioOttonelli, Massimo; Zappia, Stefania; Demartini, Anna; Alloisio, Marin