Callosal transfer of impulses originating from superficial and deep nerves of the cat forelimb.

1. Experiments were performed in 18 chloralose-anaesthetized, curarized cats in order to study the callosal transfer of somatic information originated in exteroceptive and proprioceptive receptors. Several cutaneous and deep nerves of the forelimb were prepared and stimulated with graded intensities, so as to activate selectively afferent fibres pertaining to the different groups of Lloyd's classification. Simultaneous records were taken (and averaged on-line by means of a multichannel analyzer) from the distal end of a cut dorsal rootlet (C7-C8), from the cerebral cortex (SI, SII or area 3a, according to the experiment) and from the somesthetic callosal region (SCR). 2. The low-threshold afferent fibres (Group II) of cutaneous origin were found to have a wide projection to the SCR, with the maximal density in its middle portion. Some of the fastest corticocallosal impulses are relayed monosynaptically at cortical level. Plots of the amplitude of cortical and callosal responses as a function of stimulus strength showed that both central responses have the same threshold and exhibit a parallel, sharply-rising amplitude increase, thus suggesting that the cortico-callosal re-transmission system for afferent impulses of cutaneous origin is very powerful in nature. Impulses elicited in afferent fibres of higher threshold (Group III) do not enhance the cortical and callosal positive waves provoked by Group II afferent volleys. 3. Afferent fibres of deep origin were also found to send a wide projection to the SCR, although less substantial than that of cutaneous fibres. Stimulation of the deep radial nerve elicited mass responses in the whole SCR, provided the strength of stimuli was high enough to engage the Group II fibres. Only in the central portion of the SCR were small potentials recorded in response to pure Group I volleys of DRN. Experiments performed with selective stimulation of pure muscular branches of forelimb deep nerves as well as of articular and mixed (muscular and articular) branches gave evidence making it possible to ascertain the origin of deep afferent fibres projecting to the SCR. Stimulation of the forelimb muscular branches with strength provoking full activation of Group I afferent and additional engagement of those of Group II, did not provoke mass responses in the whole extent of the SCR. In order to obtain callosal potentials upon stimulation of pure muscular nerves, it was necessary to increase the stimulus strength at or above the threshold for Group III fibres. On the contrary, the same callosal foci unresponsive to Group I and II muscular afferent volleys exhibited clear-cut responses to stimulation of the lowest-threshold Group I and/or Group II afferents of articular and mixed nerves. From the results it might be inferred that only proprioceptive information originating from articular receptors and from extrafusal muscular afferents has access to the callosal interhemispheric transfer.     

Endemism patterns in the Italian leaf beetle fauna (Coleoptera,Chrysomelidae)

In this contribution the results of a zoogeographical analysis, carried out on the 123 endemic leaf beetle species (Coleoptera: Chrysomelidae) occurring in Italy and its immediately adjacent regions, are reported. To assess the level of faunistic similarity among the different geographic regions studied, a cluster analysis was performed, based on the endemic component. This was done by calculating the Baroni Urbani & Buser’s similarity index (BUB). Finally, a parsimony analysis of endemicity (PAE) was used to identify the most important areas of endemism in Italy.     

Opposite Roles of NMDA Receptors in Relapsing and Primary Progressive Multiple Sclerosis

Synaptic transmission and plasticity mediated by NMDA receptors (NMDARs) could modulate the severity of multiple sclerosis (MS). Here the role of NMDARs in MS was first explored in 691 subjects carrying specific allelic variants of the NR1 subunit gene or of the NR2B subunit gene of this glutamate receptor. The analysis was replicated for significant SNPs in an independent sample of 1548 MS subjects. The C allele of rs4880213 was found to be associated with reduced NMDAR-mediated cortical excitability, and with increased probability of having more disability than the CT/TT MS subjects. MS severity was higher in the CC group among relapsing-remitting MS (RR-MS) patients, while primary progressive MS (PP-MS) subjects homozygous for the T allele had more pronounced clinical worsening. Mean time to first relapse, but not to an active MRI scan, was lower in the CC group of RR-MS patients, and the number of subjects with two or more clinical relapses in the first two years of the disease was higher in CC compared to CT/TT group. Furthermore, the percentage of relapses associated with residual disability was lower in subjects carrying the T allele. Lesion load at the MRI was conversely unaffected by the C or T allele of this SNP in RR-MS patients. Axonal and neuronal degeneration at the optical coherence tomography was more severe in the TT group of PP-MS patients, while reduced retinal nerve fiber thickness had less consequences on visual acuity in RR-MS patients bearing the T allele. Finally, the T allele was associated with preserved cognitive abilities at the Rao’s brief repeatable neuropsychological battery in RR-MS. Signaling through glutamate NMDARs enhances both compensatory synaptic plasticity and excitotoxic neurodegeneration, impacting in opposite ways on RR-MS and PP-MS pathophysiological mechanisms.     

A role for septin 2 in Drp1‐mediated mitochondrial fission

Mitochondria are essential eukaryotic organelles often forming intricate networks. The overall network morphology is determined by mitochondrial fusion and fission. Among the multiple mechanisms that appear to regulate mitochondrial fission, the ER and actin have recently been shown to play an important role by mediating mitochondrial constriction and promoting the action of a key fission factor, the dynamin‐like protein Drp1. Here, we report that the cytoskeletal component septin 2 is involved in Drp1‐dependent mitochondrial fission in mammalian cells. Septin 2 localizes to a subset of mitochondrial constrictions and directly binds Drp1, as shown by immunoprecipitation of the endogenous proteins and by pulldown assays with recombinant proteins. Depletion of septin 2 reduces Drp1 recruitment to mitochondria and results in hyperfused mitochondria and delayed FCCP‐induced fission. Strikingly, septin depletion also affects mitochondrial morphology in Caenorhabditis elegans, strongly suggesting that the role of septins in mitochondrial dynamics is evolutionarily conserved.     

Analyzing a randomized trial on breast self-examination with noncompliance and missing outcomes

Recently, instrumental variables methods have been used to address non-compliance in randomized experiments. Complicating such analyses is often the presence of missing data. The standard model for missing data, missing at random (MAR), has some unattractive features in this context. In this paper we compare MAR-based estimates of the complier average causal effect (CACE) with an estimator based on an alternative, nonignorable model for the missing data process, developed by Frangakis and Rubin (1999, Biometrika, 86, 365-379). We also introduce a new missing data model that, like the Frangakis-Rubin model, is specially suited for models with instrumental variables, but makes different substantive assumptions. We analyze these issues in the context of a randomized trial of breast self-examination (BSE). In the study two methods of teaching BSE, consisting of either mailed information about BSE (the standard treatment) or the attendance of a course involving theoretical and practical sessions (the new treatment), were compared with the aim of assessing whether teaching programs could increase BSE practice and improve examination skills. The study was affected by the two sources of bias mentioned above: only 55% of women assigned to receive the new treatment complied with their assignment and 35% of the women did not respond to the post-test questionnaire. Comparing the causal estimand of the new treatment using the MAR, Frangakis-Rubin, and our new approach, the results suggest that for these data the MAR assumption appears least plausible, and that the new model appears most plausible among the three choices.     

Conformational study of proteins by SAXS and EDXD: the case of trypsin and trypsinogen

The radius of gyration (Rg) of bovine trypsinogen and beta-trypsin was measured by an energy-dispersive X-ray technique (EDXD) and by small-angle X-ray scattering (SAXS), under different solvent conditions. Both techniques gave superimposable results. The experimental evidence demonstrated that: (1) no structural modifications and/or damage occurred during the data acquisition by EDXD; (2) at pH 4 the active enzyme has one class of chloride binding sites in common with the zymogen, whereas the latter protease shows an additional class able to reverse the effects on Rg induced by chloride at low concentration; and (3) the pH profile of the Rg of both proteases does not resemble at all the pH effect on beta-trypsin activity, a result in line with the finding that the electrical potentials induced by surface charge are small in absolute magnitude and produce no gradient across the active site.     

Visuomotor transformations: early cortical mechanisms of reaching

Recent studies of visually guided reaching in monkeys support the hypothesis that the visuomotor transformations underlying arm movements to spatial targets involve a parallel mechanism that simultaneously engages functionally related frontal and parietal areas linked by reciprocal cortico-cortical connections. The neurons in these areas possess similar combinations of response properties. The multimodal combinatorial properties of these neurons and the gradient architecture of the parieto-frontal network emerge as a potential substrate to link the different sensory and motor signals that arise during reaching behavior into common hybrid reference frames. This convergent combinatorial process is evident at early stages of visual information processing in the occipito-parietal cortex, suggesting the existence of re-entrant motor influences on cortical areas once believed to have only visual functions.