Excitability of the Motor Cortex in De Novo Patients with Celiac Disease

Introduction

Celiac disease (CD) may initially present as a neurological disorder or may be complicated by neurological changes. To date, neurophysiological studies aiming to an objective evaluation of the potential central nervous system involvement in CD are lacking.

Objective

To assess the profile of cortical excitability to Transcranial Magnetic Stimulation (TMS) in a group of de novo CD patients.

Materials and methods

Twenty CD patients underwent a screening for cognitive and neuropsychiatric symptoms by means of the Mini Mental State Examination and the Structured Clinical Interview for DSM-IV Axis I Disorders, respectively. Instrumental exams, including electroencephalography and brain computed tomography, were also performed. Cortico-spinal excitability was assessed by means of single and paired-pulse TMS using the first dorsal interosseus muscle of the dominant hand. TMS measures consisted of resting motor threshold, motor evoked potentials, cortical silent period (CSP), intracortical inhibition (ICI) and facilitation (ICF). None of the CD was on gluten-free diet. A group of 20 age-matched healthy controls was used for comparisons.

Results

CD showed a significantly shorter CSP (78.0 vs 125.0 ms, p<0.025), a reduced ICI (0.3 vs 0.2, p<0.045) and an enhanced ICF (1.1 vs 0.7, p<0.042) compared to controls. A dysthymic disorder was identified in five patients. The effect size between dysthymic and non-dysthymic CD patients indicated a low probability of interference with the CSP (Cohen''s d -0.414), ICI (-0.278) and ICF (-0.292) measurements.

Conclusion

A pattern of cortical excitability characterized by “disinhibition” and “hyperfacilitation” was found in CD patients. Immune system dysregulation might play a central role in triggering changes of the motor cortex excitability.     

Key analogs of a uniquely potent synthetic vinblastine that contain modifications of the C20′ ethyl substituent

A key series of vinblastine analogs 7–13, which contain modifications to the C20′ ethyl group, was prepared with use of two distinct synthetic approaches that provide modifications of the C20′ side chain containing linear and cyclized alkyl groups or added functionalized substituents. Their examination revealed the unique nature of the improved properties of the synthetic vinblastine 6, offers insights into the origins of its increased tubulin binding affinity and 10-fold improved cell growth inhibition potency, and served to probe a small hydrophobic pocket anchoring the binding of vinblastine with tubulin. Especially noteworthy were the trends observed with substitution of the terminal carbon of the ethyl group that, with the exception of 9 (R = F vs H, equipotent), led to remarkably substantial reductions in activity (>10-fold): R = F (equipotent with H) > N₃, CN (10-fold) > Me (50-fold) > Et (100-fold) > OH (inactive). This is in sharp contrast to the maintained (7) or enhanced activity (6) observed with its incorporation into a cyclic C20′/C15′-fused six-membered ring.     

Sex-Related Effects of Reproduction on Biomarkers of Oxidative Damage in Free-living Barn Swallows (Hirundo rustica)

According to life-history theory, the allocation of limiting resources to one trait has negative consequences for other traits requiring the same resource, resulting in trade-offs among life-history traits, such as reproduction and survival. In vertebrates, oxidative stress is increasingly being considered among the physiological mechanisms forming the currency of life-history trade-offs. In this study of the barn swallow (Hirundo rustica), we focus on the oxidative costs of reproduction, especially egg laying, by investigating the effects of breeding stage (pre- vs. post-laying) and progression of the season on three biomarkers of oxidative damage (OD) to plasma proteins, namely the concentration of malondialdehyde (MDA)-protein adducts and of protein thiol groups (PSH), and the protein carbonyl (PCO) content. Moreover, we investigated whether males and females differed in plasma OD levels, because the inherent sex differences in reproductive roles and physiology may originate sex-specific patterns of OD during breeding. We found that MDA-protein adduct levels were higher in the pre-laying than in the post-laying phase, that males had lower levels of MDA-modified proteins than females, and that the decline of MDA-protein adduct concentration between the pre- and the post-laying phase was more marked for females than males. In addition, MDA-protein adduct levels declined with sampling date, but only during the pre-laying phase. On the other hand, plasma PCO levels increased from the pre- to the post-laying phase in both sexes, and females had higher levels of PCO than males. PSH concentration was unaffected by breeding stage, sex or sampling date. On the whole, our findings indicate that biomarkers of protein oxidation closely track the short-term variation in breeding stage of both male and female barn swallows. Moreover, the higher protein OD levels observed among females compared to males suggest that egg laying entails oxidative costs, which might negatively affect female residual reproductive value.     

Wildfire–vegetation dynamics affect predictions of climate change impact on bird communities

Community‐level climate change indicators have been proposed to appraise the impact of global warming on community composition. However, non‐climate factors may also critically influence species distribution and biological community assembly. The aim of this paper was to study how fire–vegetation dynamics can modify our ability to predict the impact of climate change on bird communities, as described through a widely‐used climate change indicator: the community thermal index (CTI). Potential changes in bird species assemblage were predicted using the spatially‐explicit species assemblage modelling framework – SESAM – that applies successive filters to constrained predictions of richness and composition obtained by stacking species distribution models that hierarchically integrate climate change and wildfire–vegetation dynamics. We forecasted future values of CTI between current conditions and 2050, across a wide range of fire–vegetation and climate change scenarios. Fire–vegetation dynamics were simulated for Catalonia (Mediterranean basin) using a process‐based model that reproduces the spatial interaction between wildfire, vegetation dynamics and wildfire management under two IPCC climate scenarios. Net increases in CTI caused by the concomitant impact of climate warming and an increasingly severe wildfire regime were predicted. However, the overall increase in the CTI could be partially counterbalanced by forest expansion via land abandonment and efficient wildfire suppression policies. CTI is thus strongly dependent on complex interactions between climate change and fire–vegetation dynamics. The potential impacts on bird communities may be underestimated if an overestimation of richness is predicted but not constrained. Our findings highlight the need to explicitly incorporate these interactions when using indicators to interpret and forecast climate change impact in dynamic ecosystems. In fire‐prone systems, wildfire management and land‐use policies can potentially offset or heighten the effects of climate change on biological communities, offering an opportunity to address the impact of global climate change proactively.     

Cell wall-associated alpha-glucan is instrumental for Mycobacterium tuberculosis to block CD1 molecule expression and disable the function of dendritic cell derived from infected monocyte

We previously described an escape mechanism exploited by Mycobacterium tuberculosis (Mtb) to prevent the generation of fully competent dendritic cells (DC). We have now tested the effect of isolated mycobacterial components on human monocyte differentiation into DC and demonstrated that cell wall (CW)-associated alpha-glucan induces monocytes to differentiate into DC (Glu-MoDC) with the same altered phenotype and functional behaviour of DC derived from Mtb-infected monocytes (Mt-MoDC). In fact, Glu-MoDC lack CD1 molecule expression, fail to upregulate CD80 and produce IL-10 but not IL-12. We also showed that Glu-MoDC are not able to prime effector T cells or present lipid antigens to CD1-restricted T-cell clones. Thus, we propose a mechanism of Mtb-monocyte interaction mediated by CW-associated alpha-glucan, which allows the bacterium to evade both innate and acquired immune responses.     

Aquaporin-6 is expressed along the rat gastrointestinal tract and upregulated by feeding in the small intestine

Background  

Several aquaporins (a family of integral membrane proteins) have been recently identified in the mammalian gastrointestinal tract, and their involvement in the movement of fluid and small solutes has been suggested. In this direction we investigated, in some regions of the rat gastrointestinal tract, the presence and localization of aquaporin-6, given its peculiar function as an ion selective channel.     

Basement membrane deposition of nidogen 1 but not nidogen 2 requires the nidogen binding module of the laminin gamma1 chain

The nidogen-laminin interaction is proposed to play a key role in basement membrane (BM) assembly. However, though there are similarities, the phenotypes in mice lacking nidogen 1 and 2 (nidogen double null) differ to those of mice lacking the nidogen binding module (γ1III4) of the laminin γ1 chain. This indicates different cell- and tissue-specific functions for nidogens and their interaction with laminin and poses the question of whether the phenotypes in nidogen double null mice are caused by the loss of the laminin-nidogen interaction or rather by other unknown nidogen functions. To investigate this, we analyzed BMs, in particular those in the skin of mice lacking the nidogen binding module. In contrast to nidogen double null mice, all skin BMs in γ1III4-deficient mice appeared normal. Furthermore, although nidogen 1 deposition was strongly reduced, nidogen 2 appeared unchanged. Mice with additional deletion of the laminin γ3 chain, which contains a γ1-like nidogen binding module, showed a further reduction of nidogen 1 in the dermoepidermal BM; however, this again did not affect nidogen 2. This demonstrates that in vivo only nidogen 1 deposition is critically dependent on the nidogen binding modules of the laminin γ1 and γ3 chains, whereas nidogen 2 is independently recruited either by binding to an alternative site on laminin or to other BM proteins.     

Polyploidization as a retraction force in plant genome evolution: sequence rearrangements in triticale

Background

Polyploidization is a major evolutionary process in plants where hybridization and chromosome doubling induce enormous genomic stress and can generate genetic and epigenetic modifications. However, proper evaluation of DNA sequence restructuring events and the precise characterization of sequences involved are still sparse.

Methodology/Principal Findings

Inter Retrotransposons Amplified Polymorphism (IRAP), Retrotransposons Microsatellite Amplified Polymorphism (REMAP) and Inter Simple Sequence Repeat (ISSR) largely confirmed the absence of any intraspecific variation in wheat, rye and triticale. The comparative analysis of banding profiles between wheat and rye inbred lines revealed 34% of monomorphic (common to both parental species) bands for the ten different primer combinations used. The analysis of triticale plants uncovered nearly 51% of rearranged bands in the polyploid, being the majority of these modifications, due to the loss of rye bands (83%). Sequence analysis of rye fragments absent in triticale revealed for instance homology with hydroxyproline-rich glycoproteins (HRGP), a protein that belongs to a major family of inducible defence response proteins. Conversely, a wheat-specific band absent in triticale comprises a nested structure of copia-like retrotransposons elements, namely Claudia and Barbara. Sequencing of a polyploid-specific band (absent in both parents) revealed a microsatellite related sequence. Cytological studies using Fluorescent In Situ Hybridization (FISH) with REMAP products revealed a widespread distribution of retrotransposon and/or microsatellite flanking sequences on rye chromosomes, with a preferential accumulation in heterochromatic sub-telomeric domains.

Conclusions/Significance

Here, we used PCR-based molecular marker techniques involving retrotransposons and microsatellites to uncover polyploidization induced genetic restructuring in triticale. Sequence analysis of rearranged genomic fragments either from rye or wheat origin showed these to be retrotransposon-related as well as coding sequences. Further FISH analysis revealed possible chromosome hotspots for sequence rearrangements. The role of chromatin condensation on the origin of genomic rearrangements mediated by polyploidization in triticale is also discussed.