Quantification of neurodegeneration by measurement of brain-specific proteins

Quantification of neurodegeneration in animal models is typically assessed by time-consuming and observer-dependent immunocytochemistry. This study aimed to investigate if newly developed ELISA techniques could provide an observer-independent, cost-effective and time-saving tool for this purpose. Neurofilament heavy chain (NfH(SM135)), astrocytic glial fibrillary acidic protein (GFAP), S100B and ferritin, markers of axonal loss, gliosis, astrocyte activation and microglial activation, respectively, were quantified in the spinal cord homogenates of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE, n=8) and controls (n=7). Levels of GFAP were found to be threefold elevated in CREAE (13 ng/mg protein) when compared to control animals (4.5 ng/mg protein, p<0.001). The inverse was observed for NfH(SM135) (21 ng/mg protein vs. 63 ng/mg protein, p<0.001), ferritin (542 ng/mg protein vs. 858 ng/mg protein, p<0.001) and S100B (786 ng/mg protein vs. 2080 ng/mg protein, N.S.). These findings were confirmed by immunocytochemistry, which demonstrated intense staining for GFAP and decreased staining for NfH(SM135) in CREAE compared to control animals. These findings indicate that axonal loss and gliosis can be estimated biochemically using the newly developed ELISA assays for NfH(SM135) and GFAP. These assays may facilitate the quantification of pathological features involved in neurodegeneration

The new Global Multiple Sclerosis Severity Score (MSSS) correlates with axonal but not glial biomarkers

This study investigated whether the new Global Multiple Sclerosis Severity Scale (MSSS) correlated with cerebrospinal fluid biomarkers for axonal and glial pathology. The MSSS correlated with the phosphorylated neurofilament heavy chain (NfH-SMI35, R=0.44, P=0.016). The degree of neurofilament phosphorylation (ratio NfH-SMI34 to NfH-SMI35) was 8-fold higher in severely (median MSSS 6.5) versus mildly (MSSS 3.2) disabled patients (7.3 versus 0.9, P=0.03). The MSSS may provide a statistically powerful tool for comparing overall disease severity and be useful for validating the biomarker concept in MS

Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis

BACKGROUND: This study aimed to investigate if treatment response could retrospectively be related to inflammatory or axonal pathology as measured by plasma surrogate markers. METHODS: In this 1-year observational study 30 multiple sclerosis (MS) patients with relapsing-remitting disease were treated with intramuscular IFNbeta-1a or subcutaneous IFNbeta-1b. Responders and nonresponders were defined according to clinical and magnetic resonance imaging criteria. The control group consisted of 14 healthy subjects. Plasma levels of surrogate markers for inflammation (nitric oxide metabolites (NOx)), astrocytic activation (S100B) and axonal damage (NfH(SM135)) were measured using standard assays. RESULTS: There were 11 nonresponders and 19 responders to IFNbeta treatment. Median S100B levels were elevated in a higher proportion of treatment responders (63%, 42.9 pg/mL) compared to nonresponders (18%, 11.7 pg/mL, P < 0.05, Fisher's exact test) and controls (0%, 2 pg/mL, P < 0.001). Levels of NOx were found to be more frequently elevated in nonresponders (72%, 39 microM) compared to healthy controls (0%, 37 microM, P < 0.05). Levels of NfH(SM135) were more frequently elevated in responders (58%, 300 pg/mL, P < 0.001) and nonresponders (72%, 500 pg/mL, P < 0.001) compared to controls (0%, 4.5 pg/mL). CONCLUSION: Patients with relapsing-remitting MS who had surrogate marker supported evidence for astrocytic activation responded more frequently to treatment with IFNbeta

Stress, wildlife health and the conservation of a critically endangered marsupial, the woylie

When you are stressed, do you find you get sick more easily? And if you’re stressed and sick, do you feel like it takes you longer to recover

Solvent-switchable continuous-breathing behaviour in a diamondoid metal–organic framework and its influence on CO2 versus CH4 selectivity

Understanding the behaviour of flexible metal–organic frameworks (MOFs)—porous crystalline materials that undergo a structural change upon exposure to an external stimulus—underpins their design as responsive materials for specific applications, such as gas separation, molecular sensing, catalysis and drug delivery. Reversible transformations of a MOF between open- and closed-pore forms—a behaviour known as ‘breathing’—typically occur through well-defined crystallographic transitions. By contrast, continuous breathing is rare, and detailed characterization has remained very limited. Here we report a continuous-breathing mechanism that was studied by single-crystal diffraction in a MOF with a diamondoid network, (Me2NH2)[In(ABDC)2] (ABDC, 2-aminobenzene-1,4-dicarboxylate). Desolvation of the MOF in two different solvents leads to two polymorphic activated forms with very different pore openings, markedly different gas-adsorption capacities and different CO2 versus CH4 selectivities. Partial desolvation introduces a gating pressure associated with CO2 adsorption, which shows that the framework can also undergo a combination of stepped and continuous breathing

Wildlife in the line of fire: evaluating the stress physiology of a critically endangered Australian marsupial after bushfire

Australian native fauna are thought to be well adapted to fire-prone landscapes, but bushfires may still pose considerable challenges or stressors to wildlife. We investigated the impact of bushfire on the stress physiology of the woylie (brush-tailed bettong, Bettongia penicillata) a critically endangered Australian marsupial, and assessed whether fitness indices (body condition and parasite load) influenced stress physiology before and after the fire. We hypothesised that there would be a significant change in stress physiology indicators (in the form of faecal cortisol metabolites, FCM) following the fire, compared with the months previous. We trapped woylies (n≤19) at Whiteman Park Reserve in Perth, Western Australia, two days after a major bushfire and measured FCM concentration by enzyme immunoassay. Population-level comparisons of FCM were made between these samples and those collected in previous months (n≤58). While mean FCM varied by month of sample collection, it was not higher after the fire. We suggest that woylies may be able to maintain homeostasis through change (allostasis), at least in the period immediately after the fire. This is supported by our finding that FCM did not relate significantly to body condition or parasite load. Our results potentially highlight the physiological and behavioural adaptations of woylies to fire, which could be further explored in future studie

No Significant Evidence of Cognitive Biases for Emotional Stimuli in Children At-Risk of Developing Anxiety Disorders.

This paper explores whether the increased vulnerability of children of anxious parents to develop anxiety disorders may be partially explained by these children having increased cognitive biases towards threat compared with children of non-anxious parents. Parents completed questionnaires about their child’s anxiety symptoms. Children aged 5–9 (n = 85) participated in two cognitive bias tasks: 1) an emotion recognition task, and 2) an ambiguous situations questionnaire. For the emotion recognition task, there were no significant differences between at-risk children and children of non-anxious parents in their cognitive bias scores for reaction times or for accuracy in identifying angry or happy facial expressions. In addition, there were no significant differences between at-risk children and children of non-anxious parents in the number of threat interpretations made for the ambiguous situations questionnaire. It is possible that these cognitive biases only become present subsequent to the development of an anxiety disorder, or only in older at-risk children

Magnetism in Dense Quark Matter

We review the mechanisms via which an external magnetic field can affect the ground state of cold and dense quark matter. In the absence of a magnetic field, at asymptotically high densities, cold quark matter is in the Color-Flavor-Locked (CFL) phase of color superconductivity characterized by three scales: the superconducting gap, the gluon Meissner mass, and the baryonic chemical potential. When an applied magnetic field becomes comparable with each of these scales, new phases and/or condensates may emerge. They include the magnetic CFL (MCFL) phase that becomes relevant for fields of the order of the gap scale; the paramagnetic CFL, important when the field is of the order of the Meissner mass, and a spin-one condensate associated to the magnetic moment of the Cooper pairs, significant at fields of the order of the chemical potential. We discuss the equation of state (EoS) of MCFL matter for a large range of field values and consider possible applications of the magnetic effects on dense quark matter to the astrophysics of compact stars.Comment: To appear in Lect. Notes Phys. "Strongly interacting matter in magnetic fields" (Springer), edited by D. Kharzeev, K. Landsteiner, A. Schmitt, H.-U. Ye