From fix to fit into the autoptic human brains.

Formalin-fixed, paraffinembedded (FFPE) human brain tissues are very often stored in formalin for long time. Formalin fixation reduces immunostaining, and the DNA/RNA extraction from FFPE brain tissue becomes suboptimal. At present, there are different protocols of fixation and several procedures and kits to extract DNA/RNA from paraffin embedding tissue, but a gold standard protocol remains distant. In this study, we analyzed four types of fixation systems and compared histo and immuno-staining. Based on our results, we propose a modified method of combined fixation in formalin and formic acid for the autoptic adult brain to obtain easy, fast, safe and efficient immunolabelling of long-stored FFPE tissue. In particular, we have achieved an improved preservation of cellular morphology and obtained success in postmortem immunostaining for NeuN. This nuclear antigen is an important marker for mapping neurons, for example, to evaluate the histopathology of temporal lobe epilepsy or to draw the topography of cardiorespiratory brainstem nuclei in sudden infant death syndrome (SIDS). However, NeuN staining is frequently faint or lost in postmortem human brain tissues. In addition, we attained Fluoro Jade C staining, a marker of neurodegeneration, and immunofluorescent staining for stem cell antigens in the postnatal human brain, utilizing custom fit fixation procedures

Computing Macro-Effects and Welfare Costs of Temperature Volatility: A Structural Approach

We produce novel empirical evidence on the relevance of temperature volatility shocks for the dynamics of productivity, macroeconomic aggregates and asset prices. Using two centuries of UK temperature data, we document that the relationship between temperature volatility and the macroeconomy varies over time. First, the sign of the causality from temperature volatility to TFP growth is negative in the post-war period (i.e., 1950–2015) and positive before (i.e., 1800–1950). Second, over the pre-1950 (post-1950) period temperature volatility shocks positively (negatively) affect TFP growth. In the post-1950 period, temperature volatility shocks are also found to undermine equity valuations and other main macroeconomic aggregates. More importantly, temperature volatility shocks are priced in the cross section of returns and command a positive premium. We rationalize these findings within a production economy featuring long-run productivity and temperature volatility risk. In the model temperature volatility shocks generate non-negligible welfare costs. Such costs decrease (increase) when coupled with immediate technology adaptation (capital depreciation)

Polarized distribution of HCO3- transport in human normal and cystic fibrosis nasal epithelia

The polarized distribution of HCO3− transport was investigated in human nasal epithelial cells from normal and cystic fibrosis (CF) tissues. To test for HCO3− transport via conductive versus electroneutral Cl−/HCO3− exchange (anion exchange, AE) pathways, nasal cells were loaded with the pH probe 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein and mounted in a bilateral perfusion chamber. In normal, but not CF, epithelia, replacing mucosal Cl− with gluconate caused intracellular pH (pHi) to increase, and the initial rates (ΔpH min−1) of this increase were modestly augmented (∼26 %) when normal cells were pretreated with forskolin (10 μm). Recovery from this alkaline shift was dependent on mucosal Cl−, was insensitive to the AE inhibitor 4,4′-diisothiocyanatodihydrostilbene-2,2′-disulfonic acid (H2DIDS; 1.5 mm), but was sensitive to the cystic fibrosis transmembrane conductance regulator (CFTR) channel inhibitor diphenylamine-2-carboxylate (DPC; 100 μm). In contrast, removal of serosal Cl− caused pHi to alkalinize in both normal and CF epithelia. Recovery from this alkaline challenge was dependent on serosal Cl− and blocked by H2DIDS. Additional studies showed that serosally applied Ba2+ (5.0 mm) in normal, but not CF, cells induced influx of HCO3− across the apical membrane that was reversibly blocked by mucosal DPC. In a final series of studies, normal and CF cells acutely alkaline loaded by replacing bilateral Krebs bicarbonate Ringer (KBR) with Hepes-buffered Ringer solution exhibited basolateral, but not apical, recovery from an alkaline challenge that was dependent on Cl−, independent of Na+ and blocked by H2DIDS. We conclude that: (1) normal, but not CF, nasal epithelia have a constitutively active DPC-sensitive HCO3− influx/efflux pathway across the apical membrane of cells, consistent with the movement of HCO3− via CFTR; and (2) both normal and CF nasal epithelia have Na+-independent, H2DIDS-sensitive AE at their basolateral domain

Mutual Information of Population Codes and Distance Measures in Probability Space

We studied the mutual information between a stimulus and a large system consisting of stochastic, statistically independent elements that respond to a stimulus. The Mutual Information (MI) of the system saturates exponentially with system size. A theory of the rate of saturation of the MI is developed. We show that this rate is controlled by a distance function between the response probabilities induced by different stimuli. This function, which we term the {\it Confusion Distance} between two probabilities, is related to the Renyi $\alpha$-Information.Comment: 11 pages, 3 figures, accepted to PR

Neural responses to facial and vocal expressions of fear and disgust

Neuropsychological studies report more impaired responses to facial expressions of fear than disgust in people with amygdala lesions, and vice versa in people with Huntington's disease. Experiments using functional magnetic resonance imaging (fMRI) have confirmed the role of the amygdala in the response to fearful faces and have implicated the anterior insula in the response to facial expressions of disgust. We used fMRI to extend these studies to the perception of fear and disgust from both facial and vocal expressions. Consistent with neuropsychological findings, both types of fearful stimuli activated the amygdala. Facial expressions of disgust activated the anterior insula and the caudate-putamen; vocal expressions of disgust did not significantly activate either of these regions. All four types of stimuli activated the superior temporal gyrus. Our findings therefore (i) support the differential localization of the neural substrates of fear and disgust; (ii) confirm the involvement of the amygdala in the emotion of fear, whether evoked by facial or vocal expressions; (iii) confirm the involvement of the anterior insula and the striatum in reactions to facial expressions of disgust; and (iv) suggest a possible general role for the perception of emotional expressions for the superior temporal gyrus

Primary Vaginal Carcinoma Arising on Cystocele Mimicking Vulvar Cancer

Background: Primary vaginal carcinoma is a rare gynaecological tumour representing 1%–3% of all gynaecologic cancers. Several studies report increased vaginal cancer risk associated with genital prolapse following the occurrence of inflammatory lesions or decubitus ulcers. Case: We report the rare case of an 82-year-old woman with primary squamous cell carcinoma arising from vaginal wall prolapse. Vaginal carcinoma was suspected during gynaecological examination for vulvar bleeding. A wide local excision was performed and pathologic examination revealed a primary squamous cell carcinoma of the vagina. Conclusion: Persistent genital prolapse may be at risk for vaginal carcinoma, and cytological and a colposcopic assessments are essential to identify patients who require diagnostic biopsy

Characterisation of medullary astrocytic populations in respiratory nuclei and alterations in sudden unexpected death in epilepsy

Central failure of respiration during a seizure is one possible mechanism for sudden unexpected death in epilepsy (SUDEP). Neuroimaging studies indicate volume loss in the medulla in SUDEP and a post mortem study has shown reduction in neuromodulatory neuropeptidergic and monoaminergic neurones in medullary respiratory nuclear groups. Specialised glial cells identified in the medulla are considered essential for normal respiratory regulation including astrocytes with pacemaker properties in the pre-Botzinger complex and populations of subpial and perivascular astrocytes, sensitive to increased pCO2, that excite respiratory neurones. Our aim was to explore niches of medullary astrocytes in SUDEP cases compared to controls. In 48 brainstems from three groups, SUDEP (20), epilepsy controls (10) and non-epilepsy controls (18), sections through the medulla were labelled for GFAP, vimentin and functional markers, astrocytic gap junction protein connexin43 (Cx43) and adenosine A1 receptor (A1R). Regions including the ventro-lateral medulla (VLM; for the pre-Bötzinger complex), Median Raphe (MR) and lateral medullary subpial layer (MSPL) were quantified using image analysis for glial cell populations and compared between groups. Findings included morphologically and regionally distinct vimentin/Cx34-positive glial cells in the VLM and MR in close proximity to neurones. We noted a reduction of vimentin-positive glia in the VLM and MSPL and Cx43 glia in the MR in SUDEP cases compared to control groups (p < 0.05-0.005). In addition, we identified vimentin, Cx43 and A1R positive glial cells in the MSPL region which likely correspond to chemosensory glia identified experimentally. In conclusion, altered medullary glial cell populations could contribute to impaired respiratory regulatory capacity and vulnerability to SUDEP and warrant further investigation