In‐vivo Tumor detection using diffusion reflection measurements of targeted gold nanorods – a quantitative study

The ability to quantitatively and non‐invasively detect nanoparticles has important implications on their development as an in‐vivo cancer diagnostic tool. The Diffusion Reflection (DR) method is a simple, non‐invasive imaging technique which has been proven useful for the investigation of tissue's optical parameters. In this study, Monte Carlo (MC) simulations, tissue‐like phantom experiments and in‐vivo measurements of the reflected light intensity from tumor bearing mice are presented. Following intravenous injection of antibody conjugated poly (ethylene glycol)‐coated (PEGylated) gold nanorods (GNR) to tumor‐bearing mice, accumulation of GNR in the tumor was clearly detected by the DR profile of the tumor. The ability of DR measurements to quantitate in‐vivo the concentration of the GNR in the tumor was demonstrated and validated with Flame Atomic Absorption spectroscopy results. With GNR as absorbing contrast agents, DR has important potential applications in the image guided therapy of superficial tumors such as head and neck cancer, breast cancer and melanoma. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Harvest rates and foraging strategies in Negev Desert gerbils

We examined the foraging strategy and quantified the foragingtraits of two nocturnal rodent species, Allenby's gerbil (Gerbillusallenbyi) and the greater Egyptian sand gerbil (Gerbillus pyramidum).In the laboratory, both species used two distinct foragingstrategies: either they immediately consumed seeds found ina patch (seed tray); or they collected and delivered the seedsto their nest box for later consumption. Moreover, we founda transition in foraging strategy among individual G. allenbyi under laboratory conditions; they all began by consuming theseeds on the tray and, after 7 days on average, switched tothe collecting strategy. By contrast, in the field both speciesused only one foraging strategy; they collected and deliveredthe seeds to their burrow or to surface caches for later consumption.Furthermore, G. allenbyi and G. pyramidum collected seeds atsignificantly higher rates in the field than in the laboratorybecause the seed encounter rates for both species were higherin the field. This suggests that in natural conditions, probablyinvolving predation risk and competitive pressure, gerbilsmust respond in two ways: (1) they must choose a foraging strategythat reduces predation risk by minimizing time spent feedingoutside their burrows; and (2) they must forage more efficiently.In the field, seed handling time of the larger species, G. pyramidum, was shorter than that of the smaller one, G. allenbyi.This difference may give G. pyramidum an advantage when resourcelevels are high and when most of a forager's time is spent handling seeds rather than searching for more seeds. Additionally,our field study showed that the seed encounter rate of G. allenbyiwas higher than that of G. pyramidum. This difference may giveG. allenbyi an advantage when resource levels are low and whensearching occupies most of the forager's time. The differentadvantages that each species has over the other, under differentconditions, may well be factors promoting their coexistenceover a wide range of resource densities.     

Delayed puberty and hypoplastic uterus associated with hyperprolactinemia: successful treatment with bromocriptine

A 15-year-old girl referred because of primary amenorrhea was found to have a hypoplastic uterus and persistent hyperprolactinemia (72-110 ng/ml). The gonadotrophin-dependent pubertal signs, i.e. breast and vulvar development, were significantly retarded (Tanner stage 2-3) while sexual hair was well developed; bone age was 13 years. The endocrinological evaluation revealed gonadotrophin secretion (LH-basal: 0.85-1.25; peak after LH-RH: 10.4 mIU/ml; FSH-basal: 1.63-2.5; peak: 8.2 mIU/ml) and E2 levels (26-68 pg/ml) which were appropriate for Tanner stage 3. The high basal levels of PRL were nonresponsive to either stimulatory (TRH) or inhibitory (nomifensine) agents. CT scan of the brain suggested the presence of a pituitary microadenoma. Following therapy with bromocriptine (2.5 mg/day) plasma PRL levels dropped to normal (5-6.8 ng/ml) with an accompanying catch-up of pubertal development and linear growth and a marked increase in size of the uterus as documented by repeated ultrasonographic examinations. Menarche occurred 5 months after initiation of therapy, followed by regular menses thereafter. Repeated CT scan of the brain showed a decrease in the density and size of the still persisting lesion. This patient demonstrates that hyperprolactinemia can cause delayed puberty with a particular inhibitory effect on uterine growth and development.     

In vivo CH3(CH2)11SAu SAM electrodes in the beating heart: in situ analytical studies relevant to pacemakers and interstitial biosensors

To study in vivo modification of the SAM equivalent circuit when a highly ordered SAM is used as a bioelectrode, dodecanethiolate SAM-Au intramuscular electrodes were studied in living rat heart in a challenging in situ perfused rat model by impedance spectroscopy, cyclic voltammetry, and neutron activation analysis (NAA). The SAM layer experienced disintegration in vivo biological system, as NAA detected the presence of Au atoms that had leached into the surrounding living tissue. Therefore, the underlying Au surface became exposed during biological implant. Study by impedance spectroscopy, however, revealed perfect capacitive behavior for the SAM, similar to in vitro behavior. Electrodes showed a pure capacitive Nyquist plot with 86.1-89.4 degrees near-vertical line segments as the equivalent circuit locus, as for a parallel plate capacitor. Impedance magnitude varied linearly with 1/omega excluding diffusionally limited ionic charge transport. There was no diffusional conductive element Z(W infinity ) or spatially confined Warburg impedance Z(D). The effect of in vivo exposure of a highly ordered SAM is a 'sealing over' effect of new defects by the binding of proteinaceous or lipid species in the biological milieu, a fact of significance for SAM electrodes used either as pacemaker electrodes or as a platform for in vivo biosensors.     

Individual size variation and population stability in a seasonal environment: a discrete-time model and its calibration using grasshoppers

Much recent literature is concerned with how variation among individuals (e.g., variability in their traits and fates) translates into higher-level (i.e., population and community) dynamics. Although several theoretical frameworks have been devised to deal with the effects of individual variation on population dynamics, there are very few reports of empirically based estimates of the sign and magnitude of these effects. Here we describe an analytical model for size-dependent, seasonal life cycles and evaluate the effect of individual size variation on population dynamics and stability. We demonstrate that the effect of size variation on the population net reproductive rate varies in both magnitude and sign, depending on season length. We calibrate our model with field data on size- and density-dependent growth and survival of the generalist grasshopper Melanoplus femurrubrum. Under deterministic dynamics (fixed season length), size variation impairs population stability, given naturally occurring densities. However, in the stochastic case, where season length exhibits yearly fluctuations, size variation reduces the variance in population growth rates, thus enhancing stability. This occurs because the effect of size variation on net reproductive rate is dependent on season length. We discuss several limitations of the current model and outline possible routes for future model development.     

Inhaled nitric oxide induced NOS inhibition and rebound pulmonary hypertension: a role for superoxide and peroxynitrite in the intact lamb

Previous in vivo studies indicate that inhaled nitric oxide (NO) decreases nitric oxide synthase (NOS) activity and that this decrease is associated with significant increases in pulmonary vascular resistance (PVR) upon the acute withdrawal of inhaled NO (rebound pulmonary hypertension). In vitro studies suggest that superoxide and peroxynitrite production during inhaled NO therapy may mediate these effects, but in vivo data are lacking. The objective of this study was to determine the role of superoxide in the decrease in NOS activity and rebound pulmonary hypertension associated with inhaled NO therapy in vivo. In control lambs, 24 h of inhaled NO (40 ppm) decreased NOS activity by 40% (P<0.05) and increased endothelin-1 levels by 64% (P<0.05). Withdrawal of NO resulted in an acute increase in PVR (60.7%, P<0.05). Associated with these changes, superoxide and peroxynitrite levels increased more than twofold (P<0.05) following 24 h of inhaled NO therapy. However, in lambs treated with polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) during inhaled NO therapy, there was no change in NOS activity, no increase in superoxide or peroxynitrite levels, and no increase in PVR upon the withdrawal of inhaled NO. In addition, endothelial NOS nitration was 18-fold higher (P<0.05) in control lambs than in PEG-SOD-treated lambs following 24 h of inhaled NO. These data suggest that superoxide and peroxynitrite participate in the decrease in NOS activity and rebound pulmonary hypertension associated with inhaled NO therapy. Reactive oxygen species scavenging may be a useful therapeutic strategy to ameliorate alterations in endogenous NO signaling during inhaled NO therapy.     

Caught in the act: the lifetime of synaptic intermediates during the search for homology on DNA

Homologous recombination plays pivotal roles in DNA repair and in the generation of genetic diversity. To locate homologous target sequences at which strand exchange can occur within a timescale that a cell’s biology demands, a single-stranded DNA-recombinase complex must search among a large number of sequences on a genome by forming synapses with chromosomal segments of DNA. A key element in the search is the time it takes for the two sequences of DNA to be compared, i.e. the synapse lifetime. Here, we visualize for the first time fluorescently tagged individual synapses formed by RecA, a prokaryotic recombinase, and measure their lifetime as a function of synapse length and differences in sequence between the participating DNAs. Surprisingly, lifetimes can be ∼10 s long when the DNAs are fully heterologous, and much longer for partial homology, consistently with ensemble FRET measurements. Synapse lifetime increases rapidly as the length of a region of full homology at either the 3′- or 5′-ends of the invading single-stranded DNA increases above 30 bases. A few mismatches can reduce dramatically the lifetime of synapses formed with nearly homologous DNAs. These results suggest the need for facilitated homology search mechanisms to locate homology successfully within the timescales observed in vivo.