Recent evidence indicates that cyclin-dependent kinases (CDKs, cdks) may be inappropriately activated in several neurodegenerative conditions. Here, we report that cdk5 expression and activity are ...elevated after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that damages the nigrostriatal dopaminergic pathway. Supporting the pathogenic significance of the cdk5 alterations are the findings that the general cdk inhibitor, flavopiridol, or expression of dominant-negative cdk5, and to a lesser extent dominant-negative cdk2, attenuates the loss of dopaminergic neurons caused by MPTP. In addition, CDK inhibition strategies attenuate MPTP-induced hypolocomotion and markers of striatal function independent of striatal dopamine. We propose that cdk5 is a key regulator in the degeneration of dopaminergic neurons in Parkinson's disease.
We report on a study about some characteristics of muon production during the development of extended air showers initiated by ultra-high-energy cosmic rays. Using simulations with the recent new ...version of the AIRES air shower simulation system, we analyze and discuss on the observed discrepancies between experimental measurements and simulated data.
Air shower simulation programs are essential tools for the analysis of data from cosmic ray experiments and for planning the layout of new detectors. They are used to estimate the energy and mass of ...the primary particle. Unfortunately the model uncertainties translate directly into systematic errors in the energy and mass determination. Aiming at energies>10
19 eV, the models have to be extrapolated far beyond the energies available at accelerators. On the other hand, hybrid measurement of ground particle densities and calorimetric shower energy, as will be provided by the Pierre Auger Observatory, will strongly constrain shower models. While the main uncertainty of contemporary models comes from our poor knowledge of the (soft) hadronic interactions at high energies, also electromagnetic interactions, low-energy hadronic interactions and the particle transport influence details of the shower development. We review here the physics processes and some of the computational techniques of air shower models presently used for highest energies, and discuss the properties and limitations of the models.
The most severe clinical form of neurocysticercosis (NC) occurs when cysticerci are located in the subarachnoid space at the base of the brain (SaB). The diagnosis, monitoring and treatment of ...NC-SaB, constitutes a severe clinical challenge. Herein we evaluate the potential of the HP10 antigen detection enzyme-linked immunosorbent assay (HP10 Ag-ELISA) in the long term follow-up of NC-SaB cases. Assay performance was compared with that of Magnetic Resonance Imaging (MRI). In addition, the robustness of the HP10 Ag-ELISA was evaluated independently at two different institutions.
A double-blind prospective cohort trial was conducted involving 38 NC-SaB cases and a total of 108 paired serum and cerebrospinal fluid (CSF) samples taken at intervals of 4 to 8 months for up to 43 months. At each medical visit, results of sera and CSF HP10 Ag-ELISA and MRI obtained at last visit were compared and their accuracy was evaluated retrospectively, considering radiological evolution between appointments. In the long-term follow-up study, HP10 Ag-ELISA had a better agreement than MRI with retrospective radiological evaluation. High reproducibility of HP10 Ag-ELISA between laboratories was also demonstrated.
Results reported in this study establish for the first time the usefulness of the comparatively low cost HP10 Ag-ELISA for long term follow-up of NC-SaB patients.
Introduction: Neurocysticercosis (NC), a parasitic disease caused by Taenia solium, may be either asymptomatic or show a mild to severe clinical picture with intracranial hypertension. The most ...severe form of the disease is caused when viable cysticerci are localised in the ventricles or in subarachnoidal cisterns at the base of the skull. Detection of the secreted metacestode antigen HP10 in cerebrospinal fluid is a sensitive and specific method for the diagnosis of these severe NC cases. Objective and methods: To evaluate the validity of HP10 antigen detection ELISA when applied to serum, using paired serum and cerebrospinal fluid samples from 116 radiologically and clinically characterised NC patients. Results: The HP10 antigen assay exhibited a similarly high sensitivity in identifying severe NC cases from sera (84.8%) and CSF (91.3%). In contrast, HP10 antigen was rarely detected in asymptomatic or mild NC cases (3 of 57). Importantly, the HP10 antigen assay applied to serum showed high specificity (94%) when used in 126 serum samples of non-NC subjects from an endemic community with a confirmed coproparasitological diagnosis of intestinal parasitic infections. Finally, the HP10 assay also proved to be of value in the follow-up of treated patients. Conclusion: This study confirms that detection of the metacestode HP10 antigen in serum is a useful tool for diagnosis and follow-up of patients with severe forms of NC treated with cysticidal drugs.
Very energetic charm and bottom hadrons may be produced in the upper atmosphere when a primary cosmic ray or the leading hadron in an extensive air shower collide with a nucleon. At E≈108GeV their ...decay length becomes of order 10km, implying that they tend to interact in the air instead of decaying. Since the inelasticity in these collisions is much smaller than the one in proton and pion collisions, there could be rare events where a heavy-hadron component transports a significant amount of energy deep into the atmosphere. We have developed a module for the detailed simulation of these processes and have included it in a new version of the air shower simulator AIRES. We study the frequency, the energy distribution and the depth of charm and bottom production and decay in the atmosphere. As an illustration, we consider the production and decay of tau leptons (from Ds decays) and the lepton flux at PeV energies from a 30EeV proton primary. The proper inclusion of charm and bottom hadrons in AIRES opens the possibility to search for air-shower observables that are sensitive to heavy quark effects.
A lateral flow assay (LFA) for the diagnosis and monitoring of extraparenchymal neurocysticercosis, has been developed. The assay is based on the use of the monoclonal antibody HP10, and when applied ...to cerebrospinal fluid, correctly identified 34 cases of active extraparenchymal neurocysticercosis, but was negative with 26 samples from treated and cured neurocysticercosis patients and with 20 samples from unrelated neurological diseases. There was complete agreement between the HP10 Ag-ELISA results and the HP10-LFA. The HP10-LFA thus has utility for diagnosis and treatment of extraparenchymal neurocysticercosis, frequently a more dangerous form of the infection.
•Neurocysticercosis (NCC) is responsible for c.30% of preventable cases of epilepsy and 2.8 million DALY’s.•NCC is a ‘silent’ infection, characterised by late onset of neurological symptoms. Early diagnosis aids patient management.•The HP10 Ag-ELISA, using cerebrospinal fluid (CSF), detects viable NCC and importantly extraparenchymally (EP) located NCC.•A novel rapid Lateral Flow Assay (HP10-LFA) was positive for 34/34 CSF samples from viable EP-NCC cases, controls were -ve.•The HP10-LFA was positive for 34/34 CSF samples from cases of active (viable) extraparenchymal NCC and negative for a total of 46 negative control CSF samples.•This novel HP10-LFA should thus facilitate diagnosis, treatment and follow-up of NCC cases at hospital/clinic level.
Neurocysticercosis is a common parasitic disease of the human central nervous system. It is particularlyprevalent in developing countries, where it has a serious public health and economic impact. A ...major diagnostic problem with neurocysticercosis is its pleomorphic nature. Conventional diagnosis of neurocysticercosis still requires brain-computed tomography and/or magnetic resonance imaging, which are definitive but often prohibitively expensive and inaccessible in endemic areas. Herein, the monoclonal antibody HP 10 antigen-trapping enzyme-linked immunosorbent assay, which has been used successfully to detect viable Taenia solium cysticercosis, was evaluated using cerebrospinal fluid (CSF) from Mexican neurocysticercosis patients with various defined pathologies. Sensitivity was higher in cases of inflammatory compared with non-inflammatory disease (94.1% vs. 33.3%) and in cases of multiple- compared with single-cyst cysticercosis (85% vs. 33.3%). Positivity was a strong indicator of active, inflammatory, multiple-cyst neurocysticercosis detecting 100% (15/15) of such cases. The overall specificity, as determined using CSF samples from patients with other neurological symptoms, was 97.7% (42/43). Since the assay only detects viable infection, it is of known value in the follow-up of treated patients to determine whether treatment has been successful. Thus, antigen detection may be of particular value in the assessment of symptomatic patients, who may potentially benefit from rapid treatment.