Homeostasis of functional maps in active dendrites emerges in the absence of individual channelostasis

The maintenance of ion channel homeostasis, or channelostasis, is a complex puzzle in neurons with extensive dendritic arborization, encompassing a combinatorial diversity of proteins that encode these channels and their auxiliary subunits, their localization profiles, and associated signaling machinery. Despite this, neurons exhibit amazingly stereotypic, topographically continuous maps of several functional properties along their active dendritic arbor. Here, we asked whether the membrane composition of neurons, at the level of individual ion channels, is constrained by this structural requirement of sustaining several functional maps along the same topograph. We performed global sensitivity analysis on morphologically realistic conductance-based models of hippocampal pyramidal neurons that coexpressed six well-characterized functional maps along their trunk. We generated randomized models by varying 32 underlying parameters and constrained these models with quantitative experimental measurements from the soma and dendrites of hippocampal pyramidal neurons. Analyzing valid models that satisfied experimental constraints on all six functional maps, we found topographically analogous functional maps to emerge from disparate model parameters with weak pairwise correlations between parameters. Finally, we derived a methodology to assess the contribution of individual channel conductances to the various functional measurements, using virtual knockout simulations on the valid model population. We found that the virtual knockout of individual channels resulted in variable, measurement and location-specific impacts across the population. Our results suggest collective channelostasis as a mechanism behind the robust emergence of analogous functional maps and have significant ramifications for the localization and targeting of ion channels and enzymes that regulate neural coding and homeostasis.

Sparsely populated residue conformations in protein structures: Revisiting ``experimental'' Ramachandran maps

The Ramachandran map clearly delineates the regions of accessible conformational (phi-) space for amino acid residues in proteins. Experimental distributions of phi, values in high-resolution protein structures, reveal sparsely populated zones within fully allowed regions and distinct clusters in apparently disallowed regions. Conformational space has been divided into 14 distinct bins. Residues adopting these relatively rare conformations are presented and amino acid propensities for these regions are estimated. Inspection of specific examples in a completely arid, fully allowed region in the top left quadrant establishes that side-chain and backbone interactions may provide the energetic compensation necessary for populating this region of phi- space. Asn, Asp, and His residues showed the highest propensities in this region. The two distinct clusters in the bottom right quadrant which are formally disallowed on strict steric considerations correspond to the gamma turn (C7 axial) conformation (Bin 12) and the i + 1 position of Type II turns (Bin 13). Of the 516 non-Gly residues in Bin 13, 384 occupied the i + 1 position of Type II turns. Further examination of these turn segments revealed a high propensity to occur at the N-terminus of helices and as a tight turn in hairpins. The strand-helix motif with the Type II turn as a connecting element was also found in as many as 57 examples. Proteins 2014; 82:1101-1112. (c) 2013 Wiley Periodicals, Inc.

Current kinematics and dynamics of Africa and the East African Rift System

Although the East African Rift System (EARS) is an archetype continental rift, the forces driving its evolution remain debated. Some contend buoyancy forces arising from gravitational potential energy (GPE) gradients within the lithosphere drive rifting. Others argue for a major role of the diverging mantle flow associated with the African Superplume. Here we quantify the forces driving present-day continental rifting in East Africa by (1) solving the depth averaged 3-D force balance equations for 3-D deviatoric stress associated with GPE, (2) inverting for a stress field boundary condition that we interpret as originating from large-scale mantle tractions, (3) calculating dynamic velocities due to lithospheric buoyancy forces, lateral viscosity variations, and velocity boundary conditions, and (4) calculating dynamic velocities that result from the stress response of horizontal mantle tractions acting on a viscous lithosphere in Africa and surroundings. We find deviatoric stress associated with lithospheric GPE gradients are similar to 8-20 MPa in EARS, and the minimum deviatoric stress resulting from basal shear is similar to 1.6 MPa along the EARS. Our dynamic velocity calculations confirm that a force contribution from GPE gradients alone is sufficient to drive Nubia-Somalia divergence and that additional forcing from horizontal mantle tractions overestimates surface kinematics. Stresses from GPE gradients appear sufficient to sustain present-day rifting in East Africa; however, they are lower than the vertically integrated strength of the lithosphere along most of the EARS. This indicates additional processes are required to initiate rupture of continental lithosphere, but once it is initiated, lithospheric buoyancy forces are enough to maintain rifting.

PROPER HOLOMORPHIC MAPS BETWEEN BOUNDED SYMMETRIC DOMAINS REVISITED

We prove that a proper holomorphic map between two nonplanar bounded symmetric domains of the same dimension, one of them being irreducible, is a biholomorphism. Our methods allow us to give a single, all-encompassing argument that unifies the various special cases in which this result is known. We discuss an application of these methods to domains having noncompact automorphism groups that are not assumed to act transitively.

Dendritic atrophy constricts functional maps in resonance and impedance properties of hippocampal model neurons

A gradient in the density of hyperpolarization-activated cyclic-nucleotide gated (HCN) channels is necessary for the emergence of several functional maps within hippocampal pyramidal neurons. Here, we systematically analyzed the impact of dendritic atrophy on nine such functional maps, related to input resistance and local/transfer impedance properties, using conductance-based models of hippocampal pyramidal neurons. We introduced progressive dendritic atrophy in a CA1 pyramidal neuron reconstruction through a pruning algorithm, measured all functional maps in each pruned reconstruction, and arrived at functional forms for the dependence of underlying measurements on dendritic length. We found that, across frequencies, atrophied neurons responded with higher efficiency to incoming inputs, and the transfer of signals across the dendritic tree was more effective in an atrophied reconstruction. Importantly, despite the presence of identical HCN-channel density gradients, spatial gradients in input resistance, local/transfer resonance frequencies and impedance profiles were significantly constricted in reconstructions with dendrite atrophy, where these physiological measurements across dendritic locations converged to similar values. These results revealed that, in atrophied dendritic structures, the presence of an ion channel density gradient alone was insufficient to sustain homologous functional maps along the same neuronal topograph. We assessed the biophysical basis for these conclusions and found that this atrophy-induced constriction of functional maps was mediated by an enhanced spatial spread of the influence of an HCN-channel cluster in atrophied trees. These results demonstrated that the influence fields of ion channel conductances need to be localized for channel gradients to express themselves as homologous functional maps, suggesting that ion channel gradients are necessary but not sufficient for the emergence of functional maps within single neurons.

Seismic hazard maps and spectrum for Patna considering region-specific seismotectonic parameters

The objective of this paper was to develop the seismic hazard maps of Patna district considering the region-specific maximum magnitude and ground motion prediction equation (GMPEs) by worst-case deterministic and classical probabilistic approaches. Patna, located near Himalayan active seismic region has been subjected to destructive earthquakes such as 1803 and 1934 Bihar-Nepal earthquakes. Based on the past seismicity and earthquake damage distribution, linear sources and seismic events have been considered at radius of about 500 km around Patna district center. Maximum magnitude (M (max)) has been estimated based on the conventional approaches such as maximum observed magnitude (M (max) (obs) ) and/or increment of 0.5, Kijko method and regional rupture characteristics. Maximum of these three is taken as maximum probable magnitude for each source. Twenty-seven ground motion prediction equations (GMPEs) are found applicable for Patna region. Of these, suitable region-specific GMPEs are selected by performing the `efficacy test,' which makes use of log-likelihood. Maximum magnitude and selected GMPEs are used to estimate PGA and spectral acceleration at 0.2 and 1 s and mapped for worst-case deterministic approach and 2 and 10 % period of exceedance in 50 years. Furthermore, seismic hazard results are used to develop the deaggregation plot to quantify the contribution of seismic sources in terms of magnitude and distance. In this study, normalized site-specific design spectrum has been developed by dividing the hazard map into four zones based on the peak ground acceleration values. This site-specific response spectrum has been compared with recent Sikkim 2011 earthquake and Indian seismic code IS1893.

NON-DIMENSIONAL KINETOELASTOSTATIC MAPS FOR COMPLIANT MECHANISMS

How do we assess the capability of a compliant mechanism of given topology and shape? The kinetoelastostatic maps proposed in this paper help answer this question. These maps are drawn in 2D using two non-dimensional quantities, one capturing the nonlinear static response and the other the geometry, material, and applied forces. Geometrically nonlinear finite element analysis is used to create the maps for compliant mechanisms consisting of slender beams. In addition to the topology and shape, the overall proportions and the proportions of the cross-sections of the beam segments are kept fixed for a map. The finite region of the map is parameterized using a non-dimensional quantity defined as the slenderness ratio. The shape and size of the map and the parameterized curves inside it indicate the complete kinetoelastostatic capability of the corresponding compliant mechanism of given topology, shape, and fixed proportions. Static responses considered in this paper include input/output displacement, geometric amplification, mechanical advantage, maximum stress, etc. The maps can be used to compare mechanisms, to choose a suitable mechanism for an application, or re-design as may be needed. The usefulness of the non-dimensional maps is presented with multiple applications of different variety. Non-dimensional portrayal of snap-through mechanisms is one such example. The effect of the shape of the cross-section of the beam segments and the role of different segments in the mechanism as well as extension to 3D compliant mechanisms, the cases of multiple inputs and outputs, and moment loads are also explained. The effects of disproportionate changes on the maps are also analyzed.

The challenge of cancer control in Africa.

While the world is focused on controlling the spread of diseases such as HIV and malaria in the developing world, another approaching epidemic has been largely overlooked. The World Heath Organization predicts that there will be 16 million new cancer cases per year in 2020 and 70% of these will be in the developing world. Many of these cancers are preventable, or treatable when detected early enough. Establishing effective, affordable and workable cancer control plans in African countries is one step in the right direction toward limiting this epidemic.

Synchronous chaos in the coupled system of two logistic maps

Synchronous chaos is investigated in the coupled system of two Logistic maps. Although the diffusive coupling admits all synchronized motions, the stabilities of their configurations are dependent on the transverse Lyapunov exponents while independent of the longitudinal Lyapunov exponents. It is shown that synchronous chaos is structurally stable with respect to the system parameters. The mean motion is the pseudo-orbit of an individual local map so that its dynamics can be described by the local map. (C) 2004 Elsevier Ltd. All rights reserved.

The valuation of riparian fisheries in Southern and Eastern Africa

This paper reviews the published and gray literature concerning economic valuations of river fisheries in eastern and southern Africa, extracting the best available information on their direct economic values and on the impacts of changes in water management on this value. It then assesses the methods used and makes recommendations regarding approaches to be used in future. The review concentrates on rivers with their associated floodplains and major deltas. The values and issues associated with estuaries and lakes are not considered.