Immunological reactivity of a human immunodeficiency virus type I derived peptide representing a consensus sequence of the GP120 major neutralizing region V3

To reduce the opportunities for human immunodeficiency virus type 1 (HIV-1) to evade vaccine induced immunity, the development of subunit vaccines must focus on the characterization of immunogenic epitopes, which are major targets for the immune system. The most dominant site for elicitation of neutralising immune response is located on the external envelope glycoprotein gp120 within the third variable domain (V3). To overcome virus type specificity of antibodies directed to the V3-domain we designed a 36 amino acids long gp120/V3-consensus peptide (V3-C36) based on published biological data and sequence comparisons of various HIV-1 virus isolates. This peptide contains a conserved core sequence which is suggested to form a surface-exposed beta-turn. This peptide also includes T-cell epitopes defined in mice and humans, an ADCC-epitope and two highly conserved cysteine residues which were oxidized to form a cystine derivate, thus allowing correct peptide folding. In ELISA-tests, this peptide reacts with at least 90% of randomly selected sera of European and African patients infected with HIV-1 and is recognized by three different HIV-1/V3 "type-specific" antisera (MN, RF, IIIB-strain). Using this peptide as immunogen in rabbits, antisera could be raised with highly cross-reactive and HIV-1/IIIB strain neutralizing properties. Moreover, HTLV/HIV-1/IIIB specific cytotoxic T-lymphocytes (CTLs) of BALB/c mice infected with a gp120 recombinant vaccinia virus recognized the central 16- and 12-mer peptides of the V3-C36 consensus peptide in cytolytic assays, indicating perfect compatibility of the consensus peptide with the IIIB-primed CTLs. The DNA-sequence encoding the V3-consensus loop region might be an important component in newly designed recombinant subunit vaccines. In addition, due to its broad serological reactivity, the V3-consensus peptide might play an important role in special diagnostic purposes

Studies on processing, particle formation, and immunogenicity of the HIV-1 gag gene product: a possible component of a HIV vaccine

Antigens in a particulate conformation were shown to be highly immunogenic in mammals. For this reason, the particle forming capacity of derivatives of the HIV-1 group specific core antigen p55 gag was assayed and compared dependent on various expression systems: recombinant bacteria, vaccinia- and baculoviruses were established encoding the entire core protein p55 either in its authentic sequence or lacking the myristylation consensus signal. Moreover, p55 gag was expressed in combination with the protease (p55-PR) or with the entire polymerase (p55-pol), respectively. Budding of 100-160 nm p55 core particles, resembling immature HIV-virions, was observed in the eucaryotic expression systems only. In comparison to the vaccinia virus driven expression of p55 in mammalian cells, considerably higher yields of particulate core antigen were obtained by infection of Spodoptera frugiperda (Sf9) insect cells with the recombinant Autographa californica nuclear polyhedrosis (AcMNPV) baculovirus. Mutation of the NH2-terminal myristylation signal sequence prevented budding of the immature core particles. Expression of the HIV p55-PR gene construct by recombinant baculovirus resulted in complete processing of the p55 gag precursor molecule in this system. The introduction of an artificial frameshift near the natural frameshift site resulted in constitutive expression of the viral protease and complete processing of p55, both in Escherichia coli and in vaccinia virus infected cells. Interestingly, significant processing of p55 resembling that of HIV infected H9 cells could also be achieved in the vaccinia system by fusing the entire pol gene to the gag gene. Moreover, processing was not found to be dependent on amino-terminal myristylation of the gag procursor molecule, which is in contrast to observations with type C and type D retrovirus. However, complete processing of p55 into p24, p17, p9 and p6 abolished particle formation. Purified immature HIV-virus like particles were highly immunogenic in rabbits, leading to a strong humoral immune response after immunization. Empty immature p55 gag particles represent a noninfectious and attractive candidate for a basic vaccine component

Profiling soil microbial communities influenced by reduced summer precipitation and farming system history

Soil bacteria and fungi are the basis of soil food webs and contribute to a wide range of essential soil functions in arable lands. Intense land use and climate change induced reductions in summer precipitation can have varying influences on abundance, composition, and activity of microbial communities with largely unknown consequences for soil functions and plant growth including crop yields. The impact of altered precipitation patterns on soil biodiversity and associated ecosystem functions is on top of the list of eight major research gaps identified by an expert group for the European Commission still, this relationship is rarely studied under field conditions

Change of biological soil quality in organic and conventional farming systems of the DOK trial

The DOK trial has started in the 1970ies, when first reports warned us on the consequences of our actions and the limits to growth. Even though farmers and a huge research community know better, we are still not managing our soils in a sustainable way. It seems inevitable that the mainstream agriculture wants to go beyond natural frontiers. Soils have an enormous buffering capacity, but this ends, when ecosystems are collapsing not only at the local, but also at the global level

Invariant variational principle for Hamiltonian mechanics

It is shown that the action for Hamiltonian equations of motion can be brought into invariant symplectic form. In other words, it can be formulated directly in terms of the symplectic structure $\omega$ without any need to choose some 1-form $\gamma$, such that $\omega= d \gamma$, which is not unique and does not even generally exist in a global sense.Comment: final version; to appear in J.Phys.A; 17 pages, 2 figure

Many-body approach to proton emission and the role of spectroscopic factors

The process of proton emission from nuclei is studied by utilizing the two-potential approach of Gurvitz and Kalbermann in the context of the full many-body problem. A time-dependent approach is used for calculating the decay width. Starting from an initial many-body quasi-stationary state, we employ the Feshbach projection operator approach and reduce the formalism to an effective one-body problem. We show that the decay width can be expressed in terms of a one-body matrix element multiplied by a normalization factor. We demonstrate that the traditional interpretation of this normalization as the square root of a spectroscopic factor is only valid for one particular choice of projection operator. This causes no problem for the calculation of the decay width in a consistent microscopic approach, but it leads to ambiguities in the interpretation of experimental results. In particular, spectroscopic factors extracted from a comparison of the measured decay width with a calculated single-particle width may be affected.Comment: 17 pages, Revte

Influence of Soil Fertility Management on Nitrogen Mineralization, Urease Activity and Maize Yield

For studying the effect of soil fertility management practices on N mineralization, urease activity and maize yield, replicated field trials were established in 2015 at Misamfu and Msekera agricultural research stations (ARS) representing two geo-climatic regions of Zambia. The soil at Msekera ARS is a sandy clay loam (SCL) from a Paleustult, while that at Misamfu is a loamy sand (LS) from a Kandiustult. The field trials had three categories of treatments namely legumes, traditional and conventional. The legumes group consisted of researcher-recommended legume-cereal intercrop systems of maize with Cajanus cajan, Crotalaria juncea and Tephrosia vogelii in combination with compound D (10% N, 20% P2O5, 10% K2O) and urea (46% N) at the recommended rate (200 kg ha-1) and half of the recommended rate (100 kg ha-1). Composted cattle manure and Fundikila, a special plant biomass management technique, were the inputs under the traditional category. The conventional category consisted of a treatment to which only chemical fertilizer was applied. Urease activity was determined in surface soil samples (0-20 cm) collected from the field trials after 3 years. For N mineralization, a laboratory incubation study was conducted over 13 weeks. For the laboratory incubation, an additional treatment to which no input was applied was included as control. Application of organic inputs significantly increased the potentially mineralizable N (No) by 127% to 256% on the LS and by 51% to 131% on the SCL in comparison to the control. Similarly, the cumulative N mineralized (Ncum) was twice or thrice higher where organic inputs had been applied in comparison to the control. The No followed the order traditional > legumes > conventional > control, while the mineralization rate constant (k) followed the order legumes > conventional > traditional > control on both soils. The rate of N mineralization was significantly higher on the LS than the SCL. Higher rates of chemical fertilizer resulted in high Ncum and higher maize yield. Maize yield was significantly and positively correlated to Ncum, but inversely correlated to the amount of applied N that was mineralized (%Nmin). Urease activity was stimulated by application of organic inputs and suppressed by higher rates of chemical fertilizers. The type of organic inputs; the rate of chemical fertilizers; and soil texture are factors influencing N mineralization and maize yield. Urease activity was largely influenced by the rate of chemical fertilizer, but not the type of organic inputs or soil texture

Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems

Aside to clinical changes, behavioral variant frontotemporal dementia (bvFTD) is characterized by progressive structural and functional alterations in frontal and temporal regions. We examined if there is a selective vulnerability of specific neurotransmitter systems in bvFTD by evaluating the link between disease-related functional alterations and the spatial distribution of specific neurotransmitter systems and their underlying gene expression levels.Maps of fractional amplitude of low frequency fluctuations (fALFF) were derived as a measure of local activity from resting-state functional magnetic resonance imaging for 52 bvFTD patients (mean age = 61.5 ± 10.0 years; 14 female) and 22 healthy controls (HC) (mean age = 63.6 ± 11.9 years; 13 female). We tested if alterations of fALFF in patients co-localize with the non-pathological distribution of specific neurotransmitter systems and their coding mRNA gene expression. Further, we evaluated if the strength of co-localization is associated with the observed clinical symptoms.Patients displayed significantly reduced fALFF in fronto-temporal and fronto-parietal regions. These alterations co-localized with the distribution of serotonin (5-HT1b, 5-HT2a), dopamine (D2), and γ-aminobutyric acid (GABAa) receptors, the norepinephrine transporter (NET), and their encoding mRNA gene expression. The strength of co-localization with D2 and NET was associated with cognitive symptoms and disease severity of bvFTD.Local brain functional activity reductions in bvFTD followed the distribution of specific neurotransmitter systems indicating a selective vulnerability. These findings provide novel insight into the disease mechanisms underlying functional alterations. Our data-driven method opens the road to generate new hypotheses for pharmacological interventions in neurodegenerative diseases even beyond bvFTD

Predicting disease progression in behavioral variant frontotemporal dementia

Introduction: The behavioral variant of frontotemporal dementia (bvFTD) is a rare neurodegenerative disease. Reliable predictors of disease progression have not been sufficiently identified. We investigated multivariate magnetic resonance imaging (MRI) biomarker profiles for their predictive value of individual decline. Methods: One hundred five bvFTD patients were recruited from the German frontotemporal lobar degeneration (FTLD) consortium study. After defining two groups ("fast progressors" vs. "slow progressors"), we investigated the predictive value of MR brain volumes for disease progression rates performing exhaustive screenings with multivariate classification models. Results: We identified areas that predict disease progression rate within 1 year. Prediction measures revealed an overall accuracy of 80% across our 50 top classification models. Especially the pallidum, middle temporal gyrus, inferior frontal gyrus, cingulate gyrus, middle orbitofrontal gyrus, and insula occurred in these models. Discussion: Based on the revealed marker combinations an individual prognosis seems to be feasible. This might be used in clinical studies on an individualized progression model

Multiclass prediction of different dementia syndromes based on multi-centric volumetric MRI imaging

IntroductionDementia syndromes can be difficult to diagnose. We aimed at building a classifier for multiple dementia syndromes using magnetic resonance imaging (MRI).MethodsAtlas-based volumetry was performed on T1-weighted MRI data of 426 patients and 51 controls from the multi-centric German Research Consortium of Frontotemporal Lobar Degeneration including patients with behavioral variant frontotemporal dementia, Alzheimer’s disease, the three subtypes of primary progressive aphasia, i.e., semantic, logopenic and nonfluent-agrammatic variant, and the atypical parkinsonian syndromes progressive supranuclear palsy and corticobasal syndrome. Support vector machine classification was used to classify each patient group against controls (binary classification) and all seven diagnostic groups against each other in a multi-syndrome classifier (multiclass classification).ResultsThe binary classification models reached high prediction accuracies between 71 and 95% with a chance level of 50%. Feature importance reflected disease-specific atrophy patterns. The multi-syndrome model reached accuracies of more than three times higher than chance level but was far from 100%. Multi-syndrome model performance was not homogenous across dementia syndromes, with better performance in syndromes characterized by regionally specific atrophy patterns. Whereas diseases generally could be classified vs controls more correctly with increasing severity and duration, differentiation between diseases was optimal in disease-specific windows of severity and duration.DiscussionResults suggest that automated methods applied to MR imaging data can support physicians in diagnosis of dementia syndromes. It is particularly relevant for orphan diseases beside frequent syndromes such as Alzheimer’s disease