Targeting the Progression of Parkinson’s Disease

By the time a patient first presents with symptoms of Parkinson’s disease at the clinic, a significant proportion (50-70%) of the cells in the substantia nigra (SN) has already been destroyed. This degeneration progresses until, within a few years, most of the cells have died. Except for rare cases of familial PD, the initial trigger for cell loss is unknown. However, we do have some clues as to why the damage, once initiated, progresses unabated. It would represent a major advance in therapy to arrest cell loss at the stage when the patient first presents at the clinic. Current therapies for Parkinson’s disease focus on relieving the motor symptoms of the disease, these unfortunately lose their effectiveness as the neurodegeneration and symptoms progress. Many experimental approaches are currently being investigated attempting to alter the progression of the disease. These range from replacement of the lost neurons to neuroprotective therapies; each of these will be briefly discussed in this review. The main thrust of this review is to explore the interactions between dopamine, alpha synuclein and redox-active metals. There is abundant evidence suggesting that destruction of SN cells occurs as a result of a self-propagating series of reactions involving dopamine, alpha synuclein and redox-active metals. A potent reducing agent, the neurotransmitter dopamine has a central role in this scheme, acting through redox metallo-chemistry to catalyze the formation of toxic oligomers of alpha-synuclein and neurotoxic metabolites including 6-hydroxydopamine. It has been hypothesized that these feed the cycle of neurodegeneration by generating further oxidative stress. The goal of dissecting and understanding the observed pathological changes is to identify therapeutic targets to mitigate the progression of this debilitating disease

Efficacy of iron-biofortified crops

Biofortification aims to increase the content of micronutrients in staple crops without sacrificing agronomic yield, making the new varieties attractive to farmers. Food staples that provide a major energy supply in low- and middle-income populations are the primary focus. The low genetic variability of iron in the germplasm of most cereal grains is a major obstacle on the path towards nutritional impact with these crops, which is solvable only by turning to transgenic approaches. However, biofortified varieties of common beans and pearl millet have been developed successfully and made available with iron contents as high as 100 mg/kg and 80 mg/kg, respectively, two to five times greater than the levels in the regular varieties. This brief review summarizes the research to date on the bioavailability and efficacy of iron-biofortified crops, highlights their potential and limitations, and discusses the way forward with multiple biofortified crop approaches suitable for diverse cultures and socio-economic milieu. Like post-harvest iron fortification, these biofortified combinations might provide enough iron to meet the additional iron needs of many iron deficient women and children that are not covered at present by their traditional diets.Keywords: Biofortification, Iron, Beans, Pearl millet, Rice, Polyphenols, Phytic acid, Anemia, Efficacy, Nutrition-Agriculture linkage

Double-slit interference pattern from single-slit screen and its gravitational analogues

The double slit experiment (DSE) is known as an important cornerstone in the foundations of physical theories such as Quantum Mechanics and Special Relativity. A large number of different variants of it were designed and performed over the years. We perform and discuss here a new verion with the somewhat unexpected results of obtaining interference pattern from single-slit screen. This outcome, which shows that the routes of the photons through the array were changed, leads one to discuss it, using the equivalence principle, in terms of geodesics mechanics. We show using either the Brill's version of the canonical formulation of general relativity or the linearized version of it that one may find corresponding and analogous situations in the framework of general relativity.Comment: 51 pages, 12 Figures five of them contain two subfigures and thus the number of figures is 17, 1 Table. Some minor changes introduced, especially, in the reference

Electronic Structure of Transition-Metal Dicyanamides Me[N(CN)2_2]2_2 (Me = Mn, Fe, Co, Ni, Cu)

The electronic structure of Me[N(CN)$_2$]$_2$ (Me=Mn, Fe, Co, Ni, Cu) molecular magnets has been investigated using x-ray emission spectroscopy (XES) and x-ray photoelectron spectroscopy (XPS) as well as theoretical density-functional-based methods. Both theory and experiments show that the top of the valence band is dominated by Me 3d bands, while a strong hybridization between C 2p and N 2p states determines the valence band electronic structure away from the top. The 2p contributions from non-equivalent nitrogen sites have been identified using resonant inelastic x-ray scattering spectroscopy with the excitation energy tuned near the N 1s threshold. The binding energy of the Me 3d bands and the hybridization between N 2p and Me 3d states both increase in going across the row from Me = Mn to Me = Cu. Localization of the Cu 3d states also leads to weak screening of Cu 2p and 3s states, which accounts for shifts in the core 2p and 3s spectra of the transition metal atoms. Calculations indicate that the ground-state magnetic ordering, which varies across the series is largely dependent on the occupation of the metal 3d shell and that structural differences in the superexchange pathways for different compounds play a secondary role.Comment: 20 pages, 11 figures, 2 table

Fermionic SK-models with Hubbard interaction: Magnetism and electronic structure

Models with range-free frustrated Ising spin- and Hubbard interaction are treated exactly by means of the discrete time slicing method. Critical and tricritical points, correlations, and the fermion propagator, are derived as a function of temperature T, chemical potential \mu, Hubbard coupling U, and spin glass energy J. The phase diagram is obtained. Replica symmetry breaking (RSB)-effects are evaluated up to four-step order (4RSB). The use of exact relations together with the 4RSB-solutions allow to model exact solutions by interpolation. For T=0, our numerical results provide strong evidence that the exact density of states in the spin glass pseudogap regime obeys \rho(E)=const |E-E_F| for energies close to the Fermi level. Rapid convergence of \rho'(E_F) under increasing order of RSB is observed. The leading term resembles the Efros-Shklovskii Coulomb pseudogap of localized disordered fermionic systems in 2D. Beyond half filling we obtain a quadratic dependence of the fermion filling factor on the chemical potential. We find a half filling transition between a phase for U>\mu, where the Fermi level lies inside the Hubbard gap, into a phase where \mu(>U) is located at the center of the upper spin glass pseudogap (SG-gap). For \mu>U the Hubbard gap combines with the lower one of two SG-gaps (phase I), while for \mu<U it joins the sole SG-gap of the half-filling regime (phase II). We predict scaling behaviour at the continuous half filling transition. Implications of the half-filling transition between the deeper insulating phase II and phase I for delocalization due to hopping processes in itinerant model extensions are discussed and metal-insulator transition scenarios described.Comment: 29 pages, 26 Figures, 4 jpeg- and 3 gif-Fig-files include

GH peak response to GHRH-arginine: relationship to insulin resistance and other cardiovascular risk factors in a population of adults aged 50–90

OBJECTIVE: To assess the GH response to GHRH-arginine in apparently healthy adults in relation to cardiovascular risk factors. DESIGN: Cross-sectional. PATIENTS: Eighty-six male and female volunteers aged 50–90. MEASUREMENTS: GH peak response to GHRH-arginine and cardiovascular risk factors, including obesity, insulin resistance, low levels of high density lipoprotein (HDL) cholesterol, elevated triglycerides, and hypertension. The primary outcome measurement was GH response to GHRH-arginine. The relationship between GH peak responses and cardiovascular risk factors was determined after data collection. RESULTS: GH peaks were highly variable, ranging from 2·3 to 185 µg/l (14% with GH peaks < 9 µg/l). An increasing number of cardiovascular risk factors were associated with a lower mean GH peak (P < 0·0001). By univariate analysis, fasting glucose, insulin, body mass index (BMI), HDL cholesterol and triglycerides were significantly associated with GH peak (all P < 0·0001). Multiple regression analysis revealed that fasting glucose, fasting insulin, BMI, triglycerides and sex accounted for 54% of GH peak variability. The role of abdominal fat as it relates to GH peak was explored in a subset of 45 subjects. Trunk fat and abdominal subregion fat measured by dual energy X-ray absorptiometry (DXA) were inversely related to GH peak (P < 0·008 and 0·001, respectively). Analysis of this subgroup by multiple regression revealed that subregion abdominal fat became the significant obesity-related determinant of GH peak, but still lagged behind fasting insulin and glucose. CONCLUSIONS: GH response to secretagogues was highly variable in apparently healthy adults aged 50–90 years. Peak GH was significantly related to fasting glucose, insulin, BMI, HDL cholesterol, triglycerides, trunk fat and abdominal subregion fat, with fasting glucose ranking first by multiple regression analysis. There was a strong relationship between cardiovascular risk factors and low GH, with individual risk factors being additive. Although these data do not differentiate between low GH being a cause or an effect of these cardiovascular risk factors, they indicate that the relationship between low GH and increased cardiovascular risk may be physiologically important in the absence of pituitary disease

Deriving the mass of particles from Extended Theories of Gravity in LHC era

We derive a geometrical approach to produce the mass of particles that could be suitably tested at LHC. Starting from a 5D unification scheme, we show that all the known interactions could be suitably deduced as an induced symmetry breaking of the non-unitary GL(4)-group of diffeomorphisms. The deformations inducing such a breaking act as vector bosons that, depending on the gravitational mass states, can assume the role of interaction bosons like gluons, electroweak bosons or photon. The further gravitational degrees of freedom, emerging from the reduction mechanism in 4D, eliminate the hierarchy problem since generate a cut-off comparable with electroweak one at TeV scales. In this "economic" scheme, gravity should induce the other interactions in a non-perturbative way.Comment: 30 pages, 1 figur

Hamiltonian dynamics and Noether symmetries in Extended Gravity Cosmology

We discuss the Hamiltonian dynamics for cosmologies coming from Extended Theories of Gravity. In particular, minisuperspace models are taken into account searching for Noether symmetries. The existence of conserved quantities gives selection rule to recover classical behaviors in cosmic evolution according to the so called Hartle criterion, that allows to select correlated regions in the configuration space of dynamical variables. We show that such a statement works for general classes of Extended Theories of Gravity and is conformally preserved. Furthermore, the presence of Noether symmetries allows a straightforward classification of singularities that represent the points where the symmetry is broken. Examples of nonminimally coupled and higher-order models are discussed.Comment: 20 pages, Review paper to appear in EPJ

Unimodular bimode gravity and the coherent scalar-graviton field as galaxy dark matter

The explicit violation of the general gauge invariance/relativity is adopted as the origin of dark matter and dark energy of the gravitational nature. The violation of the local scale invariance alone, with the residual unimodular one, is considered. Besides the four-volume preserving deformation mode -- the transverse-tensor graviton -- the metric comprises a compression mode -- the scalar graviton, or the systolon. A unimodular invariant and general covariant metric theory of the bimode/scalar-tensor gravity is consistently worked out. To reduce the primordial ambiguity of the theory a dynamical global symmetry is imposed, with its subsequent spontaneous breaking revealed. The static spherically symmetric case in the empty, but possibly for the origin, space is studied. A three-parameter solution describing a new static space structure -- the dark lacuna -- is constructed. It enjoys the property of gravitational confinement, with the logarithmic potential of gravitational attraction at the periphery, and results in the asymptotically flat rotation curves. Comprising a super-massive dark fracture (a scalar-modified black hole) at the origin surrounded by a cored dark halo, the dark lacunas are proposed as a prototype model of galaxies, implying an ultimate account for the distributed non-gravitational matter and a putative asphericity or rotation.Comment: 38 pages, 10 figures; exposition improved, remarks added, accepted for publicatio

Multiplicity distributions at high energies as a sum of Poissonian-like distributions

It is shown that at collider energies experimental multiplicity distributions are well parameterized by a sum of Gupta-Sarma distributions. This extends earlier description of the lower energy data by the two parameter sum of Poissonians. Implications of the proposed parametrization for LHC are discussed.Comment: 16 pages, Latex, 4 EPS figure