Social cognition in multiple sclerosis: a 3-year follow-up {MRI} and behavioral study

Social cognition (SC) has become a topic of widespread interest in the last decade. SC deficits were described in multiple sclerosis (MS) patients, in association with amygdala lesions, even in those without formal cognitive impairment. In this 3-year follow-up study, we aimed at longitudinally investigating the evolution of SC deficits and amygdala damage in a group of cognitive-normal MS patients, and the association between SC and psychological well-being. After 3 years (T3) from the baseline examination (T0), 26 relapsing-remitting MS patients (RRMS) were retested with a neuropsychological battery and SC tasks (theory of mind, facial emotion recognition, empathy). A SC composite score (SCcomp) was calculated for each patient. Emotional state, fatigue, and quality of life (QoL) were also evaluated. RRMS patients at T3 underwent a 3T-MRI as performed at T0, from which were calculated both volume and cortical lesion volume (CLV) of the amygdalae. Compared to T0, at T3 all RRMS patients were still cognitive-normal and remained stable in their global SC impaired performance. At T0, SCcomp correlated with amygdala CLV (p = 0.002) while, at T3, was more associated with amygdala volume (p = 0.035) rather than amygdala CLV (p = 0.043). SCcomp change T3-T0 correlated with global emotional state (p = 0.043), depression (p = 0.046), anxiety (p = 0.034), fatigue (p = 0.025), and QoL-social functioning (p = 0.033). We showed the longitudinal stability of SC deficits in cognitive-normal RRMS patients, mirroring the amygdala structural damage and the psychological well-being. These results highlight that SC exerts a key role in M

Training-induced criticality in martensites

We propose an explanation for the self-organization towards criticality observed in martensites during the cyclic process known as `training'. The scale-free behavior originates from the interplay between the reversible phase transformation and the concurrent activity of lattice defects. The basis of the model is a continuous dynamical system on a rugged energy landscape, which in the quasi-static limit reduces to a sandpile automaton. We reproduce all the principal observations in thermally driven martensites, including power-law statistics, hysteresis shakedown, asymmetric signal shapes, and correlated disorder.Comment: 5 pages, 4 figure

Multi-lectin Affinity Chromatography and Quantitative Proteomic Analysis Reveal Differential Glycoform Levels between Prostate Cancer and Benign Prostatic Hyperplasia Sera.

Currently prostate-specific antigen is used for prostate cancer (PCa) screening, however it lacks the necessary specificity for differentiating PCa from other diseases of the prostate such as benign prostatic hyperplasia (BPH), presenting a clinical need to distinguish these cases at the molecular level. Protein glycosylation plays an important role in a number of cellular processes involved in neoplastic progression and is aberrant in PCa. In this study, we systematically interrogate the alterations in the circulating levels of hundreds of serum proteins and their glycoforms in PCa and BPH samples using multi-lectin affinity chromatography and quantitative mass spectrometry-based proteomics. Specific lectins (AAL, PHA-L and PHA-E) were used to target and chromatographically separate core-fucosylated and highly-branched protein glycoforms for analysis, as differential expression of these glycan types have been previously associated with PCa. Global levels of CD5L, CFP, C8A, BST1, and C7 were significantly increased in the PCa samples. Notable glycoform-specific alterations between BPH and PCa were identified among proteins CD163, C4A, and ATRN in the PHA-L/E fraction and among C4BPB and AZGP1 glycoforms in the AAL fraction. Despite these modest differences, substantial similarities in glycoproteomic profiles were observed between PCa and BPH sera

Phyllomedusa Venusta (Lovely Leaf Frog)

PHYLLOMEDUSA VENUSTA (Lovely Leaf Frog). DIET.Phyllomedusa venusta is an arboreal frog found in northern Colombia, the valley of Magdalena, the Darién on both sides of the ColombiaPanamá border, and western Venezuela. The species is common, but populations are decreasing due to deforestation by agricultural and livestock activities, illegal plantations, human establishments, and use of agrochemicals (Rodríguez-Mahecha et al. 2008. Guía Ilustrada de Fauna del Santuario de Vida Silvestre Los Besotes,Valledupar, Cesar, Colombia. Editorial Panamericana, Formas e Impresos, Bogotá, Colombia. 574 pp.). The food habits and many other aspects of its biology and ecology are unknown. Herein we describe the diet of P. venusta in the dry tropical forest of Colombia at three sites: 1) The Natural Reserve of Civil Society Campoalegre, Municipality Los Cordobas, Department of Cordoba (8.48502°N, 76.19520°W, WGS84; elev. 120 m); 2) Finca Los Mameyales, Municipality Piojó, Department of Atlántico (10.74480°N, 75.09279°W, WGS84; elev. 206 m); 3) Las Delicias farm, Municipality Aracataca, Department of Magdalena (10.58694°N, 74.14224°W, WGS84; elev. 197 m). We examined 28 stomachs of P. venusta collected during 0800–1200 h and 1600–1800 h within forests and disturbed areas. Samples were obtained during 2007 in the dry season (January–March), first rains (April–June), and heavy rains (September–December). SUL (mm), and maximum mouth width (mm) were recorded for each individual. We identified prey to lowest taxonomic level possible (family and genus), and their length and width were measured (complete prey only) using a digital caliper (nearest 0.1 mm). The individual volume of each prey item and the number of prey items per stomach for each prey category were recorded. Volume of each prey item was estimated using the formula of a prolate spheroid. Of the captured frogs, six were females and 22 were males (mean SUL = 67.60 ± 8.76 mm; mean mouth width = 21.76 ± 2.10 mm). The diet consisted of 16 types of prey and was dominated in volume and frequency by orthopterans. Acarina showed the highest numerical contribution (Table 1). It has been suggested that acariphagia occurs in small anurans in terrestrial habits. However, P. venusta is large and arboreal, suggesting that acariphagia is a trophic phenomenon not limited to the species defined by Simon and Toft (1991. Oikos 61:263–278). The large numbers of orthopterans and blattarians consumed are congruent with that reported for other Phyllomedusa spp. (Parmelee 1999. Sci. Pap. Nat. His. Mus. Univ. Kansas 11:1–59; Vaz-Silva et al. 2004. Herpetol. Rev. 35:160; Freitas et al. 2008. Biota Neotrop. 8:101–110). Considering the type and prey proportion, P. venusta appears to be a generalist predator with a sit-and-wait foraging strategy.Fil: Blanco Torres, Argelina. Universidad Nacional de Colombia; ColombiaFil: Duré Pitteri, Marta Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Centro de Ecología Aplicada del Litoral. Universidad Nacional del Nordeste. Centro de Ecología Aplicada del Litoral; ArgentinaFil: Bonilla, M. A.. Universidad Nacional de Colombia; Colombi

Increase of CSF inflammatory profile in a case of highly active multiple sclerosis

BACKGROUND: Clinical and imaging follow-up coupled with cerebrospinal fluid (CSF) and possibly serum profiling could provide information on disease activity and disability evolution in multiple sclerosis patients. CASE PRESENTATION: We describe the case of a relapsing-remitting MS patient whose history was characterized by failure of several therapeutic approaches and sustained disease activity. By using a highly sensitive immunoassay methodology, we examined protein expression of 70 inflammatory/cytotoxic molecules in two consecutive paired CSF and serum samples, obtained respectively in 2006 and 2013. At disease diagnosis, elevated CSF protein levels of an inflammatory pattern, including CXCL13, CXCL12, IFNγ, TNF, sTNFR1, IL8, sCD163, APRIL, BAFF, pentraxin III and MMP2 were found compared with a group of controls. At the second lumbar puncture, sustained disease activity was accompanied by considerable (more than 2 fold changes) increase expression of most of these inflammatory molecules while no significant changes in serum inflammatory markers were detected in the two consecutive serum samples. CONCLUSIONS: Elevated CSF protein expression of pro-inflammatory mediators, possibly specifically associated to GM demyelination, could remain stable or increase over time in patients with active multiple sclerosis. We underline the role of fluid analysis in understanding the pathophysiology of the disease and providing information on possible markers of disease activity and evolution

Heterogeneity of Cortical Lesion Susceptibility Mapping in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been used to characterize iron and myelin content in the deep gray matter of patients with multiple sclerosis. Our aim was to characterize the susceptibility mapping of cortical lesions in patients with MS and compare it with neuropathologic observations. MATERIALS AND METHODS: The pattern of microglial activation was studied in postmortem brain tissues from 16 patients with secondary-progressive MS and 5 age-matched controls. Thirty-six patients with MS underwent 3T MR imaging, including 3D double inversion recovery and 3D-echo-planar SWI. RESULTS: Neuropathologic analysis revealed the presence of an intense band of microglia activation close to the pial membrane in subpial cortical lesions or to the WM border of leukocortical cortical lesions. The quantitative susceptibility mapping analysis revealed 131 cortical lesions classified as hyperintense; 33, as isointense; and 84, as hypointense. Quantitative susceptibility mapping hyperintensity edge found in the proximity of the pial surface or at the white matter/gray matter interface in some of the quantitative susceptibility mapping–hyperintense cortical lesions accurately mirrors the microglia activation observed in the neuropathology analysis. CONCLUSIONS: Cortical lesion susceptibility maps are highly heterogeneous, even at individual levels. Quantitative susceptibility mapping hyperintensity edge found in proximity to the pial surface might be due to the subpial gradient of microglial activation

Phenotypic variations and chemosensitivity in small cell lung cancer

Many complex properties of cancer cells are effectively under selection within the in vivo microenvironment or following therapeutic insult. This critical combination of instability and shifting selection drives the heterogeneity of tumour cell populations in terms of many critical features. Small cell lung cancer (SCLC) is an aggressive, rapidly metastasizing neoplasm with an ability to develop resistance against chemotherapeutic agents. New SCLC therapeutic strategies are urgently needed that contain spreading disease without further compromising tumour chemosensitivity. Variants for attachment to tissue culture plastic of the NCI-H69 cell line, which grows in suspension but generates low frequency appearance of adhesion variants, were enriched, without prejudice for any specific extracellular matrix directed advantage, and then allowed for any proliferation/survival advantage in vitro to impact on the evolution of variation. Two sub-lines were generated representing two stages in variant enrichment. The developed SCLC model, which encompasses elements of variation and heterogeneity, provides opportunities to link in vitro behaviour of SCLC with in vivo characteristics with particular reference to the challenges faced in the management of SCLC such as the accrual of drug resistance. The variant model was characterized using microscopy, flow cytometry and microarray analysis, revealing variation in adherence and morphology impacting on SCLC behaviour, proliferative rate and polysialylation of the neural cell adhesion molecule. The microarray analysis has also revealed new cancer biomarkers that can be explored in clinic studies. This unique SCLC model was used to gain insights into links with chemoresistance. The studies revealed that the variant selection did not result in expansion of a drug resistant clone. Moreover, evidence of clonal evolution/selection was uncovered together with the finding of the absence of CSCs, even in enriched variants, as defined by the classical side population phenotype. The defined PSA expression patterns of the variants allowed for screening of carbohydrates-based agents for polysialylation knock-down.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Rotational symmetries of crystals with defects

I use the theory of Lie groups/algebras to discuss the symmetries of crystals with uniform distributions of defects

CSF parvalbumin levels reflect interneuron loss linked with cortical pathology in multiple sclerosis

INTRODUCTION AND METHODS: In order to verify whether parvalbumin (PVALB), a protein specifically expressed by GABAergic interneurons, could be a MS-specific marker of grey matter neurodegeneration, we performed neuropathology/molecular analysis of PVALB expression in motor cortex of 40 post-mortem progressive MS cases, with/without meningeal inflammation, and 10 control cases, in combination with cerebrospinal fluid (CSF) assessment. Analysis of CSF PVALB and neurofilaments (Nf-L) levels combined with physical/cognitive/3TMRI assessment was performed in 110 naïve MS patients and in 32 controls at time of diagnosis. RESULTS: PVALB gene expression was downregulated in MS (fold change = 3.7 ± 1.2, P < 0.001 compared to controls) reflecting the significant reduction of PVALB+ cell density in cortical lesions, to a greater extent in MS patients with high meningeal inflammation (51.8, P < 0.001). Likewise, post-mortem CSF-PVALB levels were higher in MS compared to controls (fold change = 196 ± 36, P < 0.001) and correlated with decreased PVALB+ cell density (r = -0.64, P < 0.001) and increased MHC-II+ microglia density (r = 0.74, P < 0.01), as well as with early age of onset (r = -0.69, P < 0.05), shorter time to wheelchair (r = -0.49, P < 0.05) and early age of death (r = -0.65, P < 0.01). Increased CSF-PVALB levels were detected in MS patients at diagnosis compared to controls (P = 0.002). Significant correlation was found between CSF-PVALB levels and cortical lesion number on MRI (R = 0.28, P = 0.006) and global cortical thickness (R = -0.46, P < 0.001), better than Nf-L levels. CSF-PVALB levels increased in MS patients with severe cognitive impairment (mean ± SEM:25.2 ± 7.5 ng/mL) compared to both cognitively normal (10.9 ± 2.4, P = 0.049) and mild cognitive impaired (10.1 ± 2.9, P = 0.024) patients. CONCLUSIONS: CSF-PVALB levels reflect loss of cortical interneurons in MS patients with more severe disease course and might represent an early, new MS-specific biomarker of cortical neurodegeneration, atrophy, and cognitive decline