Post-transplant cerebral toxoplasmosis diagnosed by magnetic resonance imaging.

Cerebral toxoplasmosis is a rare late complication in allogeneic bone marrow transplanted patients. Neuroradiological findings may suggest the correct diagnosis. We report a patient in whom cerebral magnetic resonance imaging (MRI) showed a lesion characteristic of toxoplasmosis. Anti- toxoplasma treatment led to clinical and radiological improvement. MRI seems to be a valid tool for detection and follow-up of cerebral toxoplasmosis

DEFAULT MODE NETWORK AND WORKING MEMORY NETWORK DURING AN FMRI WORKING MEMORY TASK: DIFFERENCES AND CORRELATIONS WITH BEHAVIORAL PERFORMANCE

INTRODUCTION Previous neuroimaging studies have shown that working memory load has marked effects on regional neural activation[1-5]. However, the mechanism through which working memory load modulates brain connectivity is still unclear. During a working memory task, two of the most involved networks are the default mode network (DMN) and the working memory network (WMN)[6-7]: the selective focus on these networks can be useful in better understanding the load effects. Spatial independent component analysis (ICA)[8] has becomes a reliable technique to investigate the networks involved during an fMRI task, as it extracts spatiotemporal patterns of neural activity maximizing spatial independence. A specific study, conducted with ICA, investigating on how the load and phase of a working memory task are related with the activation and response time, is nowadays lacking. The aim of this work is to use the time course of DMN and WMN, selected by means of ICA, for studying: a) how these networks are involved with the complexity of the task and the phase; b) how, in these networks, complexity and phase are correlated with reaction times. METHODS MR Data Acquisition and preprocessing Fifteen young adult healthy and right-handed were involved. The MR protocol consisted of one anatomical sequence 3D T1-weighted MP-RAGE (Voxel size: 1 x 1 x 1 mm) and three functional acquisitions of 15 minutes each performed with a T2*-weighted EPI sequence (TR/TE: 1500/30, In- plane resolution: 3.5x3.5 mm, Thickness: 3.5 mm, Nr of slices: 24, Field of view: 64 x 64 mm). All the images were collected with a Siemens Allegra 3T MR scanner (Siemens, Erlangen, Germany) and a standard head coil. During the fMRI acquisition the subjects performed a delayed spatial working memory paradigm presented with three levels of difficulty. The memory set consisted of one, three or five circles presented randomly in different locations and to the subjects were asked to judge whether or not a given target stimulus had been part of a previous memory stimulus set. Every experiment consisted of 90 working memory trials, 30 per load, divided in three runs. Data were analyzed with Brain Voyager QX. 2.4 (Brain Innovation, Maastricht, The Netherlands). FMRI preprocessing included: 3D head-motion correction, slice-scan time correction, spatial smoothing, temporal high pass filter and linear trend removal. Anatomic 3D data set was inhomogeneities corrected, filtered and transformed into Talairach coordinates and coregistered with the functional information. Independent Component Analysis This analysis was conducted using Brainvoyager QX 2.4. ICA analysis was performed on each subject\u2019s three functional acquisitions. A subsequent total ICA group analysis[9-10] was achieved by an inter- subject ICA group analysis of all the intra-subject ICA group analysis. From the obtained maps were selected two Independent Components (ICs) containing the WMN[1,2]: WMN1 defined by SPL and Precuneus, and WMN2 with DLPFC and IPS (Fig. 1b-c). Also one IC describing the DMN was considered, with PCC, IPL and MPFC (Fig. 1a)[11]. For each run of all the subjects the ICs time course was considered: three time windows of 3TR (4.5s) for each working memory task phase (encode, maintenance and retrieval) were selected taking into account the haemodynamic response by delaying the window of 5 volumes events from the start of every trial. The window time course was corrected for a baseline value. Mean values of the ICs where examined and a subsequent correlation between the mean values and the response time in every trial was estimated. A 3x3 two-way ANOVA on Fisher transformed correlation was conducted to test the variation of loads (load1=less complex, load3=more complex), phases and runs. Figure 1: Networks selected from ICA analysis (transversal view): (a) DMN, (b) WMN1 (c) WMN2. RESULTS Figure 2 exhibits window mean activities and correlations divided for phase and load. DMN mean activity is negative while WMN1-2 mean activities have opposite behaviors regarding the phase, but similar concerning with the complexity (Fig. 2a-c). DMN shows a reduction of the correlation from encode to retrieval, instead of WM1-2 where it grows (Fig. 2d-f). The ANOVA showed significant variation for the phases over all the subjects in WMN1-2, an interaction of the variation of phases and runs in WMN2 and a interaction of phases, runs and loads in DMN. DISCUSSION These findings suggest that working memory networks (WMNs), as isolated by means of IC A, display substantially opposed mean values related to a different areas specialization. WMN1 seems to be more involved in the first part of the mnemonic phase and the amount of this involvement is associated to the trial: the more complicated the task, the higher the activation with respect to baseline. On the other hand, WMN2 increases from the first to the last part of the trial and is probably more involved in the operation of retrieval. In Figure 2e-f it is also shown that in the retrieval there is a stronger correlation between WMN1-2 mean values and the response time probably because this phase is the more complex. DMN exhibits, over all the phases, smaller than zero mean values (due to the task inducted deactivation). In contrast, its correlation has a different trend and increases above zero during the maintenance, probably due to the free thought of this phase. The different behavior of load 3 is probably due to the fact that this type of complexity is totally different from the other two. In conclusion, this study shows that, by means of ICA, it is possible to isolate networks of connected regions and relate their time courses to task phases and behavioral performance. This is a promising approach to advance the understanding of connectivity modulations in several brain networks, including WMNs and DMN

Visual Target Modulation of Functional Connectivity Networks Revealed by Self-Organizing Group ICA

We applied a data-driven analysis based on self-organizing group independent component analysis (sogICA) to fMRI data from a three-stimulus visual oddball task. SogICA is particularly suited to the investigation of the underlying functional connectivity and does not rely on a predefined model of the experiment, which overcomes some of the limitations of hypothesis-driven analysis. Unlike most previous applications of ICA in functional imaging, our approach allows the analysis of the data at the group level, which is of particular interest in high order cognitive studies. SogICA is based on the hierarchical clustering of spatially similar independent components, derived from single subject decompositions. We identified four main clusters of components, centered on the posterior cingulate, bilateral insula, bilateral prefrontal cortex, and right posterior parietal and prefrontal cortex, consistently across all participants. Post hoc comparison of time courses revealed that insula, prefrontal cortex and right fronto-parietal components showed higher activity for targets than for distractors. Activation for distractors was higher in the posterior cingulate cortex, where deactivation was observed for targets. While our results conform to previous neuroimaging studies, they also complement conventional results by showing functional connectivity networks with unique contributions to the task that were consistent across subjects. SogICA can thus be used to probe functional networks of active cognitive tasks at the group-level and can provide additional insights to generate new hypotheses for further study

Tracking the mind's image in the brain II: Differential effects of repetitive transcranial magnetic stimulation of the right and left parietal lobe.

The functional relevance of brain activity during visuospatial tasks was investigated by combining functional magnetic resonance imaging with unilateral repetitive transcranial magnetic stimulation (rTMS). The cognitive tasks involved visuospatial operations on visually presented and mentally imagined material (“mental clock task”). While visuospatial operations were associated with activation of the intraparietal sulcus region bilaterally, only the group which received rTMS to the right parietal lobe showed an impairment of performance during and immediately after rTMS. This functional parietal asymmetry might indicate a capacity of the right parietal lobe to compensate for a temporary suppression of the left. This is compatible with current theories of spatial hemineglect and constitutes a constraint for models of distributed information processing in the parietal lobes

Degeneration and Plasticity of the Optic Pathway in Alström Syndrome.

BACKGROUND AND PURPOSE: Alstrom syndrome is a rare inherited ciliopathy in which early progressive cone-rod dystrophy leads to childhood blindness. We investigated functional and structural changes of the optic pathway in Alstrom syndrome by using MR imaging to provide insight into the underlying pathogenic mechanisms. MATERIALS AND METHODS: Eleven patients with genetically proved Alstrom syndrome (mean age, 23 years; range, 6–45 years; 5 females) and 19 age- and sex-matched controls underwent brain MR imaging. The study protocol included conventional sequences, resting-state functional MR imaging, and diffusion tensor imaging. RESULTS: In patients with Alstrom syndrome, the evaluation of the occipital regions showed the following: 1) diffuse white matter volume decrease while gray matter volume decrease spared the occipital poles (voxel-based morphometry), 2) diffuse fractional anisotropy decrease and radial diffusivity increase while mean and axial diffusivities were normal (tract-based spatial statistics), and 3) reduced connectivity in the medial visual network strikingly sparing the occipital poles (independent component analysis). After we placed seeds in both occipital poles, the seed-based analysis revealed significantly increased connectivity in patients with Alstrom syndrome toward the left frontal operculum, inferior and middle frontal gyri, and the medial portion of both thalami (left seed) and toward the anterior portion of the left insula (right and left seeds). CONCLUSIONS: The protean occipital brain changes in patients with Alstrom syndrome likely reflect the coexistence of diffuse primary myelin derangement, anterograde trans-synaptic degeneration, and complex cortical reorganization affecting the anterior and posterior visual cortex to different degrees

Defective germline reprogramming rewires the spermatogonial transcriptome.

Defective germline reprogramming in Piwil4 (Miwi2)- and Dnmt3l-deficient mice results in the failure to reestablish transposon silencing, meiotic arrest and progressive loss of spermatogonia. Here we sought to understand the molecular basis for this spermatogonial dysfunction. Through a combination of imaging, conditional genetics and transcriptome analysis, we demonstrate that germ cell elimination in the respective mutants arises as a result of defective de novo genome methylation during reprogramming rather than because of a function for the respective factors within spermatogonia. In both Miwi2-/- and Dnmt3l-/- spermatogonia, the intracisternal-A particle (IAP) family of endogenous retroviruses is derepressed, but, in contrast to meiotic cells, DNA damage is not observed. Instead, we find that unmethylated IAP promoters rewire the spermatogonial transcriptome by driving expression of neighboring genes. Finally, spermatogonial numbers, proliferation and differentiation are altered in Miwi2-/- and Dnmt3l-/- mice. In summary, defective reprogramming deregulates the spermatogonial transcriptome and may underlie spermatogonial dysfunction

Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.

International audienceThe mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure

Properties of an alkali-thermo stable xylanase from Geobacillus thermodenitrificans A333 and applicability in xylooligosaccharides generation

An extracellular thermo-alkali-stable and cellulase-free xylanase from Geobacillus thermodenitrificans A333 was purified to homogeneity by ion exchange and size exclusion chromatography. Its molecular mass was 44 kDa as estimated in native and denaturing conditions by gel filtration and SDS-PAGE analysis, respectively. The xylanase (GtXyn) exhibited maximum activity at 70 °C and pH 7.5. It was stable over broad ranges of temperature and pH retaining 88 % of activity at 60 °C and up to 97 % in the pH range 7.5–10.0 after 24 h. Moreover, the enzyme was active up to 3.0 M sodium chloride concentration, exhibiting at that value 70 % residual activity after 1 h. The presence of other metal ions did not affect the activity with the sole exceptions of K+ that showed a stimulating effect, and Fe2+, Co2+ and Hg2+, which inhibited the enzyme. The xylanase was activated by non-ionic surfactants and was stable in organic solvents remaining fully active over 24 h of incubation in 40 % ethanol at 25 °C. Furthermore, the enzyme was resistant to most of the neutral and alkaline proteases tested. The enzyme was active only on xylan, showing no marked preference towards xylans from different origins. The hydrolysis of beechwood xylan and agriculture-based biomass materials yielded xylooligosaccharides with a polymerization degree ranging from 2 to 6 units and xylobiose and xylotriose as main products. These properties indicate G. thermodenitrificans A333 xylanase as a promising candidate for several biotechnological applications, such as xylooligosaccharides preparation

Advanced Virgo Plus: Future Perspectives

While completing the commissioning phase to prepare the Virgo interferometer for the next joint Observation Run (O4), the Virgo collaboration is also finalizing the design of the next upgrades to the detector to be employed in the following Observation Run (O5). The major upgrade will concern decreasing the thermal noise limit, which will imply using very large test masses and increased laser beam size. But this will not be the only upgrade to be implemented in the break between the O4 and O5 observation runs to increase the Virgo detector strain sensitivity. The paper will cover the challenges linked to this upgrade and implications on the detector's reach and observational potential, reflecting the talk given at 12th Cosmic Ray International Seminar - CRIS 2022 held in September 2022 in Napoli