Cortical activations in humans grasp-related areas depend on hand used and handedness

Background

In non-human primates grasp-related sensorimotor transformations are accomplished in a circuit involving the anterior intraparietal sulcus (area AIP) and both the ventral and the dorsal sectors of the premotor cortex (vPMC and dPMC, respectively). Although a human homologue of such a circuit has been identified whether activity within this circuit varies depending on handedness has yet to be investigated.

Methodology/Principal Findings

We used functional magnetic resonance imaging (fMRI) to explicitly test how handedness modulates activity within human grasping-related brain areas. Right- and left-handers subjects were requested to reach towards and grasp an object with either the right or the left hand using a precision grip while scanned. A kinematic study was conducted with similar procedures as a behavioral counterpart for the fMRI experiment. Results from a factorial design revealed significant activity within the right dPMC, the right cerebellum and AIP bilaterally. The pattern of activity within these areas mirrored the results found for the behavioral study.

Conclusion/Significance

Data are discussed in terms of an handedness-independent role for the right dPMC in monitoring hand shaping, the need for bilateral AIP activity for the performance of precision grip movements which varies depending on handedness and the involvement of the cerebellum in terms of its connections with AIP. These results provide the first compelling evidence of specific grasping related neural activity depending on handedness.     

Rev-Independent Simian Immunodeficiency Virus Strains Are Nonpathogenic in Neonatal Macaques

The viral protein Rev is essential for the export of the subset of unspliced and partially spliced lentiviral mRNAs and the production of structural proteins. Rev and its RNA binding site RRE can be replaced in both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) by the constitutive RNA transport element CTE of the simian type D retroviruses. We used neonatal macaques as a sensitive animal model to evaluate the pathogenicity of a pair of SIV mutant strains generated from Rev-independent molecular clones of SIVmac239 which differ only in the presence of the nef open reading frame. After high primary viremia, all animals remained persistently infected at levels below the threshold of detection. All macaques infected as neonates developed normally, and none showed any signs of immune dysfunction or disease during follow-up ranging from 2.3 to 4 years. Therefore, the Rev-RRE regulatory mechanism plays a key role in the maintenance of high levels of virus propagation, which is independent of the presence of nef. These data demonstrate that Rev regulation plays an important role in the pathogenicity of SIV. Replacement of Rev-RRE by the CTE provides a novel approach to dramatically lower the virulence of a pathogenic lentivirus. These data further suggest that antiretroviral strategies leading to even a partial block of Rev function may modulate disease progression in HIV-infected individuals.     

Airborne fungal spores colonising marbles exposed in the terrace of Messina Museum, Sicily

Studies were carried out on the air and on Carraramarble blocks located in the terrace of MessinaMuseum, in order to know the likelihood of airbornefungal spores coming into contact with and colonisingtridimensional objects. Our results showed there were not significantdifferences between airborne fungi circulating inspring and in autumn; Aspergillus, Penicillium,Fusarium, Alternaria, Cladosporium,Ulocladium, Aureobasidium, Phoma were themost common isolates. However, only few species wereable to settle on the marble surfaces as demonstratedby their isolation after 2 and 6 years of exposition.     

In vitro poly(ADP‐ribosyl)ated histones H1a and H1t modulate rat testis chromatin condensation differently

Rat testis H1 proteins were poly(ADP‐ribosyl)ated in vitro. The modifying product, poly(ADP‐ribose), was found covalently bound to each histone variant at various extents and exhibited distinct structural features (linear and short, rather than branched and long chains). Interest was focused on the somatic H1a, particularly abundant in the testis, as compared with other tissues, and the testis‐specific H1t, which appears only at the pachytene spermatocyte stage of germ cell development. These H1s were modified with poly(ADP‐ribose) by means of two in vitro experimental approaches. In the first system, each variant was incubated with purified rat testis poly(ADP‐ribose)polymerase in the presence of [³²P] NAD. In parallel, poly(ADP‐ribosyl)ated H1s were also prepared following incubation of intact rat testis nuclei with [³²P] NAD. In both experiments, the poly(ADP‐ribosyl)ated proteins were purified from the native forms by means of phenyl boronic agarose chromatography. The results from both analyses were in agreement and showed qualitative differences with regard to the poly(ADP‐ribose) covalently associated with H1a and H1t. Comparison of the bound polymers clearly indicated that the oligomers associated with H1a were within 10–12 units long, whereas longer chains (≤20 ADP‐R units) were linked to H1t. Individual poly(ADP‐ribosyl)ated H1s were complexed with homologous H1‐depleted oligonucleosomes (0.5–2.5 kbp) in order to measure their ability to condensate chromatin, in comparison with the native ones. Circular dichroism showed that the negative charges of the oligomeric polyanion, although present in limited numbers, highly influenced the DNA‐binding properties of the analyzed H1s. In particular, the poly(ADP‐ribosyl)ated H1a and H1t had opposite effects on the condensation of H1‐depleted oligonucleosomes. J. Cell. Biochem. 76:20–29, 1999. © 1999 Wiley‐Liss, Inc.     

Stereoselectivity in central analgesic action of tocainide and its analogs

The antiarrhythmic drug tocainide (5a) and some related chiral α-amino and α-imino anilides (5b–e) were synthesized in optically active form. The antinociceptive effects of the different stereoisomers of these compounds were examined and it was found that the analgesic effect of tocainide is due only to its (?)-(R)-enantiomer. Benzyl replacement for methyl group at the stereogenic centre of tocainide causes loss of activity while both enantiomers of the αiminoxilidide 5e and of the strictly related tocainide analog 5d produce an analgesic effect without any stereoselectivity. Pharmacological tests and [³H] quinuclidinyl benzilate ([³H]QNB) binding assay, taken together, seem to show that the antinociceptive effect of (?)-(R)-tocainide, like the analgesia induced by lidocaine, procaine, and mexiletine, is due to a central presynaptic cholinergic mechanism of action. © 1993 Wiley-Liss, Inc.     

Toxicity and genotoxicity of surface water before and after various potabilization steps

Many studies have revealed the presence of compounds with genotoxic activity in drinking water by means of short-term mutagenicity tests. In this study, the influence of the different steps of surface water treatment on the mutagenicity of drinking water was evaluated. Four different types of samples were collected: raw lake water, water after pre-disinfection with chlorine dioxide, water after filtration on granular activated carbon, and tap water. Water extracts underwent a bacterial toxicity test (Microtox test) and different in vitro genotoxicity tests: a test with Salmonella typhimurium strains, a Saccharomyces cerevisiae test, the SOS Chromotest with Escherichia coli and the Mutatox test with Vibrio fischeri. The Microtox test revealed high toxicity in the treated water samples. The disinfection steps increased the toxicity: the Mutatox test confirmed these results and the Salmonella/microsome test at the highest doses showed toxicity that could conceal mutagenicity. The SOS Chromotest was positive in all treated water samples without metabolic activation. In the test with S. cerevisiae both toxicity and genotoxicity generally increased during the water treatment steps, especially in cells without induction of cytochrome P450.     

Structural determinants of unexpected agonist activity in a retro-peptide analogue of the SDF-1alpha N-terminus

We have synthesised two retro-peptide analogues of the stromal cell derived growth factor 1 (SDF-1alpha) segment known to be critical for CXCR4 receptor binding, corresponding to the sequences HSEFFRCPCRFFESH and HSEFFRGGGRFFESH. We have assayed the ability of these peptides to activate extracellular signal-regulated kinase 1/2 phosphorylation in cells over expressing the SDF-1alpha receptor, finding that the first variant was able to serve as an agonist of CXCR4, whereas the second one was inactive. Finally, by comparing representative solution structures of the two peptides, we have found that the biological response of HSEFFRCPCRFFESH may be ascribed to a beta-beta-type turn motif centred on Phe(4)-Phe(5).