bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic engineering of sugars and simple sugar derivatives in plants
Authors: W. Patrick John , C. Botha Frikkie , G. Birch Robert
Published: October 2012

Carbon captured through photosynthesis is transported, and sometimes stored in plants, as sugar. All organic compounds in plants trace to carbon from sugars, so sugar metabolism is highly regulated and integrated with development. Sugars stored by plants are important to humans as foods and as renewable feedstocks for industrial conversion to biofuels and biomaterials. For some purposes, sugars have advantages over polymers including starches, cellulose or storage lipids. This review considers progress and prospects in plant metabolic engineering for increased yield of endogenous sugars and for direct production of higher‐value sugars and simple sugar derivatives. Opportunities are examined for enhancing export of sugars from leaves. Focus then turns to manipulation of sugar metabolism in sugar‐storing sink organs such as fruits, sugarcane culms and sugarbeet tubers. Results from manipulation of suspected ‘limiting’ enzymes indicate a need for clearer understanding of flux control mechanisms, to achieve enhanced levels of endogenous sugars in crops that are highly selected for this trait. Outcomes from in planta conversion to novel sugars and derivatives range from severe interference with plant development to field demonstration of crops accumulating higher‐value sugars at high yields. The differences depend on underlying biological factors including the effects of the novel products on endogenous metabolism, and on biotechnological fine‐tuning including developmental expression and compartmentation patterns. Ultimately, osmotic activity may limit the accumulation of sugars to yields below those achievable using polymers; but results indicate the potential for increases above current commercial sugar yields, through metabolic engineering underpinned by improved understanding of plant sugar metabolism.
Enhanced rates of herbicide metabolism in low herbicide‐dose selected resistant Lolium rigidum
Authors: YU Q. , HAN H. , CAWTHRAY G. R. , WANG S. F. , POWLES S. B.
Published: October 2012

Lolium rigidum is an obligately cross‐pollinated, genetically diverse species and an economically important herbicide resistance‐prone weed. Our previous work has demonstrated that recurrent selection of initially susceptible L. rigidum populations with low herbicide rates results in rapid herbicide resistance evolution. Here we report on the mechanisms endowing low‐dose‐selected diclofop‐methyl resistance in L. rigidum. Results showed that resistance was not due to target‐site ACCase mutations or overproduction, or differential herbicide leaf uptake and translocation. The in vivo de‐esterification of diclofop‐methyl into phytotoxic diclofop acid was rapid and similar in resistant versus susceptible populations. However, further metabolism of diclofop acid into non‐toxic metabolites was always faster in resistant plants than susceptible plants, resulting in up to 2.6‐fold lower level of diclofop acid in resistant plants. This corresponded well with up to twofold higher level of diclofop acid metabolites in resistant plants. The major polar metabolites of diclofop acid chromatographically resembled those of wheat, a naturally tolerant species. Clearly, recurrent selection at reduced herbicide rates selected for non‐target‐site‐based enhanced rates of herbicide metabolism, likely involving cytochrome P450 monooxygenases.
Light acclimation, retrograde signalling, cell death and immune defences in plants
Authors: KARPIŃSKI STANISŁAW , SZECHYŃSKA‐HEBDA MAGDALENA , WITUSZYŃSKA WERONIKA , BURDIAK PAWEŁ
Published: October 2012

This review confronts the classical view of plant immune defence and light acclimation with recently published data. Earlier findings have linked plant immune defences to nucleotide‐binding site leucine‐rich repeat (NBS‐LRR)‐dependent recognition of pathogen effectors and to the role of plasma membrane‐localized NADPH‐dependent oxidoreductase (AtRbohD), reactive oxygen species (ROS) and salicylic acid (SA). However, recent results suggest that plant immune defence also depends on the absorption of excessive light energy and photorespiration. Rapid changes in light intensity and quality often cause the absorption of energy, which is in excess of that required for photosynthesis. Such excessive light energy is considered to be a factor triggering photoinhibition and disturbance in ROS/hormonal homeostasis, which leads to cell death in foliar tissues. We highlight here the tight crosstalk between ROS‐ and SA‐dependent pathways leading to light acclimation, and defence responses leading to pathogen resistance. We also show that LESION SIMULATING DISEASE 1 (LSD1) regulates and integrates these processes. Moreover, we discuss the role of plastid–nucleus signal transduction, photorespiration, photoelectrochemical signalling and ‘light memory’ in the regulation of acclimation and immune defence responses. All of these results suggest that plants have evolved a genetic system that simultaneously regulates systemic acquired resistance (SAR), cell death and systemic acquired acclimation (SAA).
A putative role for TIP and PIP aquaporins in dynamics of leaf hydraulic and stomatal conductances in grapevine under water stress and re‐watering
Authors: POU ALICIA , MEDRANO HIPOLITO , FLEXAS JAUME , TYERMAN STEPHEN D.
Published: October 2012

We examined the role of aquaporins (AQPs) in regulating leaf hydraulic conductance (Kleaf) in Vitis vinifera L. (cv Chardonnay) by studying effects of AQP inhibitors, and AQP gene expression during water stress (WS) and recovery (REC). Kleaf was measured after 3 h of petiole perfusion with different solutions and to introduce inhibitors. The addition of 0.1 mm HgCl2 to 15 mm KCl reduced Kleaf compared with perfusion in 15 mM KNO3 or KCl, and these solutions were used for leaves from control, WS and REC plants. Perfusion for 3 h did not significantly alter stomatal conductance (gs) though expression of VvTIP1;1 was increased. WS decreased Kleaf by about 30% and was correlated with gs. The expression of VvTIP2;1 and VvPIP2;1 correlated with Kleaf, and VvTIP2;1 was highly correlated with gs. There was no association between the expression of particular AQPs during WS and REC and inhibition of Kleaf by HgCl2; however, HgCl2 treatment itself increased expression of VvPIP2;3 and decreased expression of VvPIP2;1. Inhibition by HgCl2 of Kleaf only at early stages of WS and then after REC suggested that apoplasmic pathways become more important during WS. This was confirmed using fluorescent dyes confined to apoplasm or preferentially accumulated in symplasm.
Maternal Exposure to High Temperatures Disrupts OCT4 mRNA Expression of Rabbit Pre‐Implantation Embryos and Endometrial Tissue
Authors: Marco‐Jiménez F , Naturil‐Alfonso C , Peñaranda DS , Jiménez‐Trigos E , García‐Diego FJ , Vicente JS
Published: October 2012

Contents

We examined the effect of prolonged high heat stress on reproductive performance and its relationship with gene expression in pre‐implantation embryos and endometrial tissue. In experiment 1, primiparous rabbit does were divided into two environments: control does (maintained between 14 and 22°C) and heat‐treated does housed in a climatic chamber (maintained between 25 and 35°C). Females were reproducing, and the litter size and live born kits were assessed at 2nd and 3rd partum. In heat‐treated does, lower litter size (9.7 ± 0.48 and 11.4 ± 0.50) and fewer live born kits (7.2 ± 0.55 and 10.2 ± 0.57) were observed, although similar ovulation rates and numbers of pre‐implantation embryos were noted. In experiment 2, after 3rd partum multiparous non‐lactating does from each experimental group were used to obtain pre‐implantation embryos and endometrial tissue. mRNA transcripts from OCT‐4, VEGF, erbB3, Ifn‐ɣ, HSP70 and HSP90 were analysed by real‐time qPCR. Higher values of OCT‐4 expression were observed in embryos and endometrial tissue in females reproduced under heat conditions. Moreover, elevated temperatures have been shown to up‐regulate VEGF in embryos and down‐regulate Ifn‐ɣ in endometrial tissue. The findings suggest a deleterious temperature effect on litter size and live born kits as a consequence of variation in gene expression pattern of the pre‐implantational embryo and the endometrium associated with proliferation and differentiation and probably with implantation and uterine and foetal development during gestation.
Exploratory study of the typology of various grades of mature skin
Authors: Sainthillier Jean‐Marie , Mac‐Mary Sophie , Monnier Delphine , Mermet Perrine , Tarrit Cécile , Mudry Carine , Humbert Philippe
Published: October 2012

Background

Post‐menopausal skin aging has intrinsic as well as extrinsic origins, and this process induces important disparities of appearance and feeling within an age range.

Objective

The objective of this study was to identify 3 grades of maturity of the facial skin of menopausal women.

Material and Method

One hundred and fifty women aged between 50 and 80 (63 ± 7 years) were enrolled. The investigations combined clinical scoring, biometrological measurements (corneometry, cutometry, digital photography, and 3D analysis by fringe projection), and questionnaires. Images elaborated from photographs and 3D views were scored by 2 investigators to classify the subjects according to 3 grades of skin maturity.

Results

STEPDISC statistical analysis revealed that the most relevant variables to differentiate the maturity grades were elastosis, wrinkles on the cheeks, wrinkles on the upper lip, roughness, spots, and elasticity.

Conclusion

The age does not reveal the degree of maturity of mature skin. Three grades of skin maturity in menopausal women, based on clinical and physiological patterns, have been differentiated in this study. Cosmetic treatments specifically adapted to the needs of menopausal women can therefore be developed.
Myosin VI has a One Track Mind Versus Myosin Va When Moving on Actin Bundles or at an Intersection
Authors: Ali M. Yusuf , Previs Samantha B. , Trybus Kathleen M. , Sweeney H. Lee , Warshaw David M.
Published: October 2012

Myosin VI (myoVI) and myosin Va (myoVa) serve roles both as intracellular cargo transporters and tethers/anchors. In both capacities, these motors bind to and processively travel along the actin cytoskeleton, a network of intersecting actin filaments and bundles that present directional challenges to these motors. Are myoVI and myoVa inherently different in their abilities to interact and maneuver through the complexities of the actin cytoskeleton? Thus, we created an in vitro model system of intersecting actin filaments and individual unipolar (fascin‐actin) or mixed polarity (α‐actinin‐actin) bundles. The stepping dynamics of individual Qdot‐labeled myoVI and myoVa motors were determined on these actin tracks. Interestingly, myoVI prefers to stay on the actin filament it is traveling on, while myoVa switches filaments with higher probability at an intersection or between filaments in a bundle. The structural basis for this maneuverability difference was assessed by expressing a myoVI chimera in which the single myoVI IQ was replaced with the longer, six IQ myoVa lever. The mutant behaved more like myoVI at actin intersections and on bundles, suggesting that a structural element other than the lever arm dictates myoVI's preference to stay on track, which may be critical to its role as an intracellular anchor.
Efficient implementation of the Hardy–Ramanujan–Rademacher formula
Authors: Johansson Fredrik
Published: October 2012

We describe how the Hardy–Ramanujan–Rademacher formula can be implemented to allow the partition function p(n) to be computed with softly optimal complexity O(n1/2+o(1)) and very little overhead. A new implementation based on these techniques achieves speedups in excess of a factor 500 over previously published software and has been used by the author to calculate p(1019), an exponent twice as large as in previously reported computations. We also investigate performance for multi-evaluation of p(n), where our implementation of the Hardy–Ramanujan–Rademacher formula becomes superior to power series methods on far denser sets of indices than previous implementations. As an application, we determine over 22 billion new congruences for the partition function, extending Weaver’s tabulation of 76 065 congruences. Supplementary materials are available with this article.
A TRP among the astrocytes
Authors: Scimemi Annalisa
Published: October 2012

Abstract  TRP channels were first identified as membrane proteins mediating phototransduction in fruit flies. Astrocytes were initially referred to as the silent elements of the nervous system. At the time these discoveries were made, few would have suspected TRP channels and astrocytes could contribute significantly to our understanding of brain signalling. Recent findings, however, put TRP channels and astrocytes in the spotlight, describe their ability to modulate the activity of specific sets of synapses, and raise some interesting questions. What makes astrocytes capable of exerting cell‐specific effects on interneuronal signals? How do different synapses respond to changes in astrocytic function and in the local micro‐structure of the neuropil? Can astrocytes be considered good candidate targets for therapeutic intervention to treat neurological diseases? Here I discuss the recent developments on TRP channels and astrocytes that have made us aware of the many structural and functional features of synapses that still need to be discovered and that could lead a new avant‐garde in decoding the cellular and molecular basis of brain (dys)function.
Constriction of isolated collecting lymphatic vessels in response to acute increases in downstream pressure
Authors: Scallan Joshua P. , Wolpers John H. , Davis Michael J.
Published: October 2012

Key points

Arterioles undergo a myogenic constriction, defined as a decrease in diameter in response to an increase in pressure, which serves to protect the downstream capillaries from changes in pressure and flow.

A lymphatic constriction was recently identified but it remained unknown whether it reflected a true myogenic constriction.

By selectively raising downstream pressure in isolated lymphatic vessels containing a single valve, we discovered that the upstream segment constricted, even when protected from increases in pressure by the closed valve. The constriction consisted of a myogenic component and a frequency component, which were blocked pharmacologically.

The lymphatic constriction facilitated proper closure of the intraluminal valves in the face of a hydrostatic gradient, preventing lymph backflow.

This work adds to our understanding of the lymphatic myogenic constriction by showing that it maintains a functioning valve system in lymphatic vessels and that it is mechanistically similar to the arteriolar myogenic constriction.

Abstract  Collecting lymphatic vessels generate pressure to transport lymph downstream to the subclavian vein against a significant pressure head. To investigate their response to elevated downstream pressure, collecting lymphatic vessels containing one valve (incomplete lymphangion) or two valves (complete lymphangion) were isolated from the rat mesentery and tied to glass cannulae capable of independent pressure control. Downstream pressure was selectively raised to various levels, either stepwise or ramp‐wise, while keeping upstream pressure constant. Diameter and valve positions were tracked under video microscopy, while intralymphangion pressure was measured concurrently with a servo‐null micropipette. Surprisingly, a potent lymphatic constriction occurred in response to the downstream pressure gradient due to (1) a pressure‐dependent myogenic constriction and (2) a frequency‐dependent decrease in diastolic diameter. The myogenic index of the lymphatic constriction (−3.3 ± 0.6, in mmHg) was greater than that of arterioles or collecting lymphatic vessels exposed to uniform increases in pressure (i.e. upstream and downstream pressures raised together). Additionally, the constriction was transmitted to the upstream lymphatic vessel segment even though it was protected from changes in pressure by a closed intraluminal valve; the conducted constriction was blocked by loading only the pressurized half of the vessel with either ML‐7 (0.5 mm) to block contraction, or cromakalim (3 μm) to hyperpolarize the downstream muscle layer. Finally, we provide evidence that the lymphatic constriction is important to maintain normal intraluminal valve closure during each contraction cycle in the face of an adverse pressure gradient, which probably protects the lymphatic capillaries from lymph backflow.
T‐type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control
Authors: Mariotta Luca , Ramadan Tamara , Singer Dustin , Guetg Adriano , Herzog Brigitte , Stoeger Claudia , Palacín Manuel , Lahoutte Tony , Camargo Simone M. R. , Verrey François
Published: October 2012

Key points

The amino acid (AA) transporter TAT1 (Slc16A10) mediates facilitated diffusion of aromatic AAs (AAAs) across membranes.

TAT1 null mice lack liver control of AAAs and display altered epithelial AA transport.

The data support the hypothesis that equilibrative transport of essential AAs by TAT1 is crucial for body AA homeostasis control.

Abstract  The uniporter TAT1 (Slc16a10) mediates the facilitated diffusion of aromatic amino acids (AAAs) across basolateral membranes of kidney, small intestine and liver epithelial cells, and across the plasma membrane of non‐epithelial cells like skeletal myocytes. Its role for body AA homeostasis has now been investigated using newly generated TAT1 (Slc16a10) defective mice (tat1−/−). These mice grow and reproduce normally, show no gross phenotype and no obvious neurological defect. Histological analysis did not reveal abnormalities and there is no compensatory change in any tested AA transporter mRNA. TAT1 null mice, however, display increased plasma, muscle and kidney AAA concentration under both normal and high protein diet, although this concentration remains normal in the liver. A major aromatic aminoaciduria and a smaller urinary loss of all substrates additionally transported by l‐type AA antiporter Lat2–4F2hc (Slc7a8) were revealed under a high protein diet. This suggests an epithelial transport defect as also shown by the accumulation of intravenously injected 123I‐2‐I‐l‐Phe in kidney and l‐[3H]Phe in ex vivo everted gut sac enterocytes. Taken together, these data indicate that the uniporter TAT1 is required to equilibrate the concentration of AAAs across specific membranes. For instance, it enables hepatocytes to function as a sink that controls the extracellular AAAs concentration. Additionally, it facilitates the release of AAAs across the basolateral membrane of small intestine and proximal kidney tubule epithelial cells, thereby allowing the efflux of other neutral AAs presumably via Lat2–4F2hc.
Distinct localization and modulation of Cav1.2 and Cav1.3 L‐type Ca2+ channels in mouse sinoatrial node
Authors: Christel Carl J. , Cardona Natalia , Mesirca Pietro , Herrmann Stefan , Hofmann Franz , Striessnig Joerg , Ludwig Andreas , Mangoni Matteo E. , Lee Amy
Published: October 2012

Key points

In the sinoatrial node (SAN), Cav1 voltage‐gated Ca2+ channels mediate L‐type currents that are essential for normal cardiac pacemaking.

Both Cav1.2 and Cav1.3 Ca2+ channels are expressed in the SAN but how their distinct properties affect cardiac pacemaking is unknown.

Here, we show that unlike Cav1.2, Cav1.3 undergoes voltage‐dependent facilitation and colocalizes with ryanodine receptors in sarcomeric structures.

By mathematical modelling, these properties of Cav1.3 can improve recovery of pacemaking after pauses and stabilize SAN pacemaking during excessively slow heart rates.

We conclude that voltage‐dependent facilitation and colocalization with ryanodine receptors distinguish Cav1.3 from Cav1.2 channels in the SAN and contribute to the major impact of Cav1.3 on pacemaking.

Abstract  Dysregulation of L‐type Ca2+ currents in sinoatrial nodal (SAN) cells causes cardiac arrhythmia. Both Cav1.2 and Cav1.3 channels mediate sinoatrial L‐type currents. Whether these channels exhibit differences in modulation and localization, which could affect their contribution to pacemaking, is unknown. In this study, we characterized voltage‐dependent facilitation (VDF) and subcellular localization of Cav1.2 and Cav1.3 channels in mouse SAN cells and determined how these properties of Cav1.3 affect sinoatrial pacemaking in a mathematical model. Whole cell Ba2+ currents were recorded from SAN cells from mice carrying a point mutation that renders Cav1.2 channels relatively insensitive to dihydropyridine antagonists. The Cav1.2‐mediated current was isolated in the presence of nimodipine (1 μm), which was subtracted from the total current to yield the Cav1.3 component. With strong depolarizations (+80 mV), Cav1.2 underwent significantly stronger inactivation than Cav1.3. VDF of Cav1.3 was evident during recovery from inactivation at a time when Cav1.2 remained inactivated. By immunofluorescence, Cav1.3 colocalized with ryanodine receptors in sarcomeric structures while Cav1.2 was largely restricted to the delimiting plasma membrane. Cav1.3 VDF enhanced recovery of pacemaker activity after pauses and positively regulated pacemaking during slow heart rate in a numerical model of mouse SAN automaticity, including preferential coupling of Cav1.3 to ryanodine receptor‐mediated Ca2+ release. We conclude that strong VDF and colocalization with ryanodine receptors in mouse SAN cells are unique properties that may underlie a specific role for Cav1.3 in opposing abnormal slowing of heart rate.
Contribution of non‐endothelium‐dependent substances to exercise hyperaemia: are they O2 dependent?
Authors: Marshall Janice M. , Ray Clare J.
Published: October 2012

Abstract  This review considers the contributions to exercise hyperaemia of substances released into the interstitial fluid, with emphasis on whether they are endothelium dependent or O2 dependent. The early phase of exercise hyperaemia is attributable to K+ released from contracting muscle fibres and acting extraluminally on arterioles. Hyperpolarization of vascular smooth muscle and endothelial cells induced by K+ may also facilitate the maintained phase, for example by facilitating conduction of dilator signals upstream. ATP is released into the interstitium from muscle fibres, at least in part through cystic fibrosis transmembrane conductance regulator‐associated channels, following the fall in intracellular H+. ATP is metabolized by ectonucleotidases to adenosine, which dilates arterioles via A2A receptors, in a nitric oxide‐independent manner. Evidence is presented that the rise in arterial achieved by breathing 40% O2 attenuates efflux of H+ and lactate, thereby decreasing the contribution that adenosine makes to exercise hyperaemia; efflux of inorganic phosphate and its contribution may likewise be attenuated. Prostaglandins (PGs), PGE2 and PGI2, also accumulate in the interstitium during exercise, and breathing 40% O2 abolished the contribution of PGs to exercise hyperaemia. This suggests that PGE2 released from muscle fibres and PGI2 released from capillaries and venular endothelium by a fall in their local act extraluminally to dilate arterioles. Although modest hyperoxia attenuates exercise hyperaemia by improving O2 supply, limiting the release of O2‐dependent adenosine and PGs, higher O2 concentrations may have adverse effects. Evidence is presented that breathing 100% O2 limits exercise hyperaemia by generating O2−, which inactivates nitric oxide and decreases PG synthesis.
Does sex have an independent effect on thermoeffector responses during exercise in the heat?
Authors: Gagnon Daniel , Kenny Glen P.
Published: October 2012

Abstract  Although a number of studies have examined potential differences in temperature regulation between males and females during heat stress, conclusions have remained limited as to whether reported differences are due to confounding physical characteristics or to actual differences in the physiological variables of temperature regulation. Recent observations suggest that sex differences in temperature regulation, particularly in sudomotor activity, go beyond those associated with physical characteristics. Females have recently been shown to have a lower sudomotor activity, as well as a lower thermosensitivity of the response compared to males during exercise performed at a fixed rate of metabolic heat production. Furthermore, sex differences in local and whole‐body sudomotor activity are only evident above a certain combination of environmental conditions and rate of metabolic heat production. In contrast, both the onset threshold and thermosensitivity of cutaneous vasodilatation are similar between males and females. In theory, differences in the thermosensitivity of sudomotor activity could be related to either a central (neural activity/integration) and/or peripheral (effector organ) modulation of temperature regulation. Based on recent findings, sex differences in sudomotor activity appear to be mediated peripherally, although a central modulation has yet to be conclusively ruled out. Here we present a brief yet comprehensive review of the current state of knowledge pertaining to sex differences in temperature regulation during exercise in the heat.
Cell intrinsic and extrinsic factors contribute to enhance neural circuit reconstruction following transplantation in Parkinsonian mice
Authors: Kauhausen Jessica , Thompson Lachlan H. , Parish Clare L.
Published: October 2012

Key points

Ectopic cell transplantation for Parkinson's disease improves dopamine neurotransmission but fails to restore the neural circuit important for controlled motor function, and may thereby underlie suboptimal and variable outcomes in patients. However, homotopic grafts, into the site of cell loss, survive poorly and show limited integration.

Here we explore intrinsic and extrinsic factors to improve homotopic grafting.

The use of fetal donor tissue, younger than conventionally used, generates significantly larger grafts with increased innervation and circuit reconstruction. These effects can be enhanced by exposure of the graft to glial derived neurotrophic factor.

Furthermore, improved homotypic grafts are capable of enhancing functional recovery in Parkinsonian mice.

These findings have important implications for the development of cell‐ and stem cell‐based therapies to promote neural circuit reconstruction in the treatment of Parkinson's disease.

Abstract  Cell replacement therapy for Parkinson's disease has predominantly focused on ectopic transplantation of fetal dopamine (DA) neurons into the striatum as a means to restore neurotransmission, rather than homotopic grafts into the site of cell loss, which would require extensive axonal growth. However, ectopic grafts fail to restore important aspects of DA circuitry necessary for controlled basal ganglia output, and this may underlie the suboptimal and variable functional outcomes in patients. We recently showed that DA neurons in homotopic allografts of embryonic ventral mesencephalon (VM) can send long axonal projections along the nigrostriatal pathway in order to innervate forebrain targets, although the extent of striatal reinnervation remains substantially less than can be achieved with ectopic placement directly into the striatal target. Here, we examined the possible benefits of using younger VM donor tissue and over‐expression of glial cell‐derived neurotrophic factor (GDNF) in the striatal target to improve the degree of striatal innervation from homotopic grafts. Younger donor tissue, collected on embryonic day (E)10, generated 4‐fold larger grafts with greater striatal targeting, compared to grafts generated from more conventional E12 donor VM. Over‐expression of GDNF in the host brain also significantly increased DA axonal growth and striatal innervation. Furthermore, a notable increase in the number and proportion of A9 DA neurons, essential for functional recovery, was observed in younger donor grafts treated with GDNF. Behavioural testing confirmed functional integration of younger donor tissue and demonstrated that improved motor function could be attributed to both local midbrain and striatal innervation. Together, these findings suggest there is significant scope for further development of intra‐nigral grafting as a restorative approach for Parkinson's disease.
Effect of p-AlxGa1−xN electron blocking layer on optical and electrical properties in GaN-based light emitting diodes
Authors: Kim Ki-Hyun , Lee Sang-Won , Lee Sung-Nam , Kim Jihoon
Published: October 2012

The authors investigated the effect of p-type AlGaN electron blocking layer (EBL) on the optical and the electrical properties of GaN-based blue light-emitting diodes. 405- and 325-nm photoluminescence (PL) analyses showed the maximum intensities from 18% and 12% p-AlGaN EBL, respectively. Both PL methods would make a clear distinction between the optical qualities of InGaN well and the carrier transport from n-/p-type layers to active layer. From electroluminescence (EL) measurement, it found that the highest EL intensity was obtained at 12% p-AlGaN EBL, which was consistent with the result of 325-nm PL. From these results, the authors concluded that the 12% p-AlGaN EBL would effectively suppress the carrier overflow and that the problem for carrier transport was dominant at a higher than 18% Al in p-AlGaN EBL by measuring 325-nm PL and the photogenerated current.
Unfolding linac photon spectra and incident electron energies from experimental transmission data, with direct independent validation
Authors: Ali E. S. M. , McEwen M. R. , Rogers D. W. O.
Published: October 2012

Purpose:

In a recent computational study, an improved physics‐based approach was proposed for unfolding linac photon spectra and incident electron energies from transmission data. In this approach, energy differentiation is improved by simultaneously using transmission data for multiple attenuators and detectors, and the unfolding robustness is improved by using a four‐parameter functional form to describe the photon spectrum. The purpose of the current study is to validate this approach experimentally, and to demonstrate its application on a typical clinical linac.

Methods:

The validation makes use of the recent transmission measurements performed on the Vickers research linac of National Research Council Canada. For this linac, the photon spectra were previously measured using a NaI detector, and the incident electron parameters are independently known. The transmission data are for eight beams in the range 10–30 MV using thick Be, Al and Pb bremsstrahlung targets. To demonstrate the approach on a typical clinical linac, new measurements are performed on an ElektaPrecise linac for 6, 10 and 25 MV beams. The different experimental setups are modeled using EGSnrc, with the newly added photonuclear attenuation included.

Results:

For the validation on the research linac, the 95% confidence bounds of the unfolded spectra fall within the noise of the NaI data. The unfolded spectra agree with theEGSnrc spectra (calculated using independently known electron parameters) with RMS energy fluence deviations of 4.5%. The accuracy of unfolding the incident electron energy is shown to be ∼3%. A transmission cutoff of only 10% is suitable for accurate unfolding, provided that the other components of the proposed approach are implemented. For the demonstration on a clinical linac, the unfolded incident electron energies and their 68% confidence bounds for the 6, 10 and 25 MV beams are 6.1 ± 0.1, 9.3 ± 0.1, and 19.3 ± 0.2 MeV, respectively. The unfolded spectra for the clinical linac agree with the EGSnrc spectra (calculated using the unfolded electron energies) with RMS energy fluence deviations of 3.7%. The corresponding measured and EGSnrc‐calculated transmission data agree within 1.5%, where the typical transmission measurement uncertainty on the clinical linac is 0.4% (not including the uncertainties on the incident electron parameters).

Conclusions:

The approach proposed in an earlier study for unfolding photon spectra and incident electron energies from transmission data is accurate and practical for clinical use.
Technical Note: Precision and accuracy of a commercially available CT optically stimulated luminescent dosimetry system for the measurement of CT dose index
Authors: Vrieze Thomas J. , Sturchio Glenn M. , McCollough Cynthia H.
Published: October 2012

Purpose:

To determine the precision and accuracy of CTDI100 measurements made using commercially available optically stimulated luminescent (OSL) dosimeters (Landaur, Inc.) as beam width, tube potential, and attenuating material were varied.

Methods:

One hundred forty OSL dosimeters were individually exposed to a single axial CT scan, either in air, a 16‐cm (head), or 32‐cm (body) CTDI phantom at both center and peripheral positions. Scans were performed using nominal total beam widths of 3.6, 6, 19.2, and 28.8 mm at 120 kV and 28.8 mm at 80 kV. Five measurements were made for each of 28 parameter combinations. Measurements were made under the same conditions using a 100‐mm long CTDI ion chamber. Exposed OSL dosimeters were returned to the manufacturer, who reported dose to air (in mGy) as a function of distance along the probe, integrated dose, and CTDI100.

Results:

The mean precision averaged over 28 datasets containing five measurements each was 1.4% ± 0.6%, range = 0.6%–2.7% for OSL and 0.08% ± 0.06%, range = 0.02%–0.3% for ion chamber. The root mean square (RMS) percent differences between OSL and ion chamber CTDI100 values were 13.8%, 6.4%, and 8.7% for in‐air, head, and body measurements, respectively, with an overall RMS percent difference of 10.1%. OSL underestimated CTDI100 relative to the ion chamber 21/28 times (75%). After manual correction of the 80 kV measurements, the RMS percent differences between OSL and ion chamber measurements were 9.9% and 10.0% for 80 and 120 kV, respectively.

Conclusions:

Measurements of CTDI100 with commercially available CT OSL dosimeters had a percent standard deviation of 1.4%. After energy‐dependent correction factors were applied, the RMS percent difference in the measured CTDI100 values was about 10%, with a tendency of OSL to underestimate CTDI relative to the ion chamber. Unlike ion chamber methods, however, OSL dosimeters allow measurement of the radiation dose profile.
Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove
Authors: Garai Ágnes , Zeke András , Gógl Gergő , Törő Imre , Fördős Ferenc , Blankenburg Hagen , Bárkai Tünde , Varga János , Alexa Anita , Emig Dorothea , Albrecht Mario , Reményi Attila
Published: October 2012

Three related kinases use distinct structural features to discriminate between linear docking motifs in potential binding partners.
Interferon-Induced SCYL2 Limits Release of HIV-1 by Triggering PP2A-Mediated Dephosphorylation of the Viral Protein Vpu
Authors: Miyakawa Kei , Sawasaki Tatsuya , Matsunaga Satoko , Tokarev Andrey , Quinn Gary , Kimura Hirokazu , Nomaguchi Masako , Adachi Akio , Yamamoto Naoki , Guatelli John , Ryo Akihide
Published: October 2012

HIV-infected cells dephosphorylate and inactivate a viral factor to restrict viral spreading.
Posttraumatic Stress Disorder in Children and Adolescents: Neuroendocrine PerspectivesA Presentation from the European Society for Paediatric Endocrinology (ESPE) New Inroads to Child Health (NICHe) Conference on Stress Response and Child Health in Heraklion, Crete, Greece, 18 to 20 May 2012.
Authors: Pervanidou Panagiota , Chrousos George P.
Published: October 2012

Trauma-induced changes in circulating cortisol concentrations are associated with pediatric PTSD.
Science Signaling
Podcast: 9 October 2012
Authors: Nestler Eric J. , VanHook Annalisa M.
Published: October 2012

The neurotrophic factor BDNF has opposite effects on cocaine- and morphine-induced neuroplasticity.
Regulating Opioid Responses
Authors: Stern Peter R.
Published: October 2012

Morphine reward is modulated by ventral tegmental area BDNF in a way that is opposite to its modulation of cocaine reward.
Defining a Linear Ubiquitin-Binding Domain
Authors: Gough Nancy R.
Published: October 2012

Binding of the seventh zinc finger of A20 to linear ubiquitin chains is another mechanism by which A20 inhibits activation of nuclear factor κB.
Tasting Amino Acids Limits Autophagy
Authors: Wong Wei
Published: October 2012

A taste receptor complex acts as an amino acid sensor for mTORC1.
Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
Authors: Pea Federico , Viale Pierluigi , Cojutti Piergiorgio , Furlanut Mario
Published: October 2012

The worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producing
Enterobacteriaceae
has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL
Cr
) estimates for use in daily clinical practice to target the steady-state concentrations (
C
ss
s) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CL
m
) and CL
Cr
was retrospectively assessed in a cohort of critically ill patients (group 1,
n
= 67) to create a formula for dosage calculation to target
C
ss
. The performance of this formula was validated in a similar cohort (group 2,
n
= 56) by comparison of the observed and the predicted
C
ss
s. A significant relationship between CL
m
and CL
Cr
was observed in group 1 (
r
= 0.72,
P
< 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) = [0.078 × CL
Cr
(ml/min) + 2.85] × target
C
ss
× (24/1,000), led to a significant correlation between the observed and the predicted
C
ss
s (
r
= 0.92,
P
< 0.001). Dosing nomograms based on CL
Cr
were created to target the meropenem
C
ss
at 8, 12, and 16 mg/liter in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline susceptible pathogens or even of carbapenemase producers and/or of pathophysiological conditions which may enhance meropenem clearance.
Genetic Markers of Widespread Extensively Drug-Resistant Pseudomonas aeruginosa High-Risk Clones
Authors: Cabot Gabriel , Ocampo-Sosa Alain A. , Domínguez M. Angeles , Gago Juan F. , Juan Carlos , Tubau Fe , Rodríguez Cristina , Moyà Bartolomé , Peña Carmen , Martínez-Martínez Luis , Oliver Antonio
Published: October 2012

Recent reports have revealed the existence of widespread extensively drug-resistant (XDR)
P. aeruginosa
high-risk clones in health care settings, but there is still scarce information on their specific chromosomal (mutational) and acquired resistance mechanisms. Up to 20 (10.5%) of 190 bloodstream isolates collected from 10 Spanish hospitals met the XDR criteria. A representative number (15 per group) of isolates classified as multidrug-resistant (MDR) (22.6%), resistant to 1 to 2 classes (moderately resistant [modR]) (23.7%), or susceptible to all antibiotics (multiS) (43.2%) were investigated in parallel. Multilocus sequence typing (MLST) analysis revealed that all XDR isolates belonged to sequence type 175 (ST175) (
n
= 19) or ST111 (
n
= 1), both recognized as international high-risk clones. Clonal diversity was higher among the 15 MDR isolates (4 ST175, 2 ST111, and 8 additional STs) and especially high among the 15 modR (13 different STs) and multiS (14 STs) isolates. The XDR/MDR pattern in ST111 isolates correlated with the production of VIM-2, but none of the ST175 isolates produced acquired β-lactamases. In contrast, the analysis of resistance markers in 12 representative isolates (from 7 hospitals) of ST175 revealed that the XDR pattern was driven by the combination of AmpC hyperproduction, OprD inactivation (Q142X), 3 mutations conferring high-level fluoroquinolone resistance (GyrA T83I and D87N and ParC S87W), a G195E mutation in MexZ (involved in MexXY-OprM overexpression), and the production of a class 1 integron harboring the
aadB
gene (gentamicin and tobramycin resistance). Of particular interest, in nearly all the ST175 isolates, AmpC hyperproduction was driven by a novel AmpR-activating mutation (G154R), as demonstrated by complementation studies using an
ampR
mutant of PAO1. This work is the first to describe the specific resistance markers of widespread
P. aeruginosa
XDR high-risk clones producing invasive infections.
Feed-Forward Regulation of Phagocytosis by Entamoeba histolytica
Authors: Sateriale Adam , Vaithilingam Archana , Donnelly Liam , Miller Peter , Huston Christopher D.
Published: October 2012

The parasitic protozoanEntamoeba histolyticais aptly named for its capacity to destroy host tissue. WhenE. histolyticatrophozoites invade the lamina propria of a host colon, extracellular matrices are degraded while host cells are killed and phagocytosed. The ability ofE. histolyticato phagocytose host cells correlates with virulencein vivo. In order to better understand the mechanism of phagocytosis, we used anE. histolyticaAffymetrix microarray chip to measure the total gene expression of phagocytic and nonphagocytic subpopulations. Using paramagnetic beads coated with a known host ligand that stimulates phagocytosis, phagocytic and nonphagocytic amoebae from a single culture were purified. Microarray analysis of the subpopulations identified 121 genes with >2-fold higher expression in phagocytic than in nonphagocytic amoebae. Functional annotation identified genes encoding proteins involved in actin binding and cytoskeletal organization as highly enriched gene clusters.Post hocanalyses of selected genes showed that the gene expression profile identified in the microarray experiment did not exist prior to cell sorting but rather was stimulated through phagocytosis. Further, these expression profiles correlated with an increase in phagocytic ability, asE. histolyticacultures exposed to an initial stimulus of phagocytosis showed increased phagocytic ability upon a second stimulus. To our knowledge, this is the first description of such feed-forward regulation of gene expression and phagocytic ability in a phagocyte.
Antivirulence Genes: Insights into Pathogen Evolution through Gene Loss
Authors: Bliven Kimberly A. , Maurelli Anthony T.
Published: October 2012

The emergence of new pathogens and the exploitation of novel pathogenic niches by bacteria typically require the horizontal transfer of virulence factors and subsequent adaptation—a “fine-tuning” process—for the successful incorporation of these factors into the microbe's genome. The function of newly acquired virulence factors may be hindered by the expression of genes already present in the bacterium. Occasionally, certain genes must be inactivated or deleted for full expression of the pathogen phenotype to occur. These genes are known as antivirulence genes (AVGs). Originally identified in
Shigella
, AVGs have improved our understanding of pathogen evolution and provided a novel approach to drug and vaccine development. In this review, we revisit the AVG definition and update the list of known AVGs, which now includes genes from pathogens such as
Salmonella
,
Yersinia pestis
, and the virulent
Francisella tularensis
subspecies. AVGs encompass a wide variety of different roles within the microbe, including genes involved in metabolism, biofilm synthesis, lipopolysaccharide modification, and host vasoconstriction. More recently, the use of one of these AVGs (
lpxL
) as a potential vaccine candidate highlights the practical application of studying AVG inactivation in microbial pathogens.
Nasopharyngeal tuberculosis presenting with auditory symptoms: Figure 1
Authors: Pankhania Miran , Elloy Marianne , Conboy Peter J
Published: October 2012

We present an unusual case of a 54-year-old Chinese lady presenting to the ears, nose and throat clinic after family members noticed that her hearing had progressively deteriorated over the preceding weeks. She also complained of tinnitus. Examination of the ears, nose and throat was unremarkable. Flexible nasoendoscopy demonstrated swelling in the postnasal space, which, following biopsy, was shown to be pathognomonic of tuberculosis. This was successfully treated with multidisciplinary input and the patient made a complete recovery.
Challenges in management of complex panic disorder in a palliative care setting
Authors: Udo Itoro , Gash Amanda
Published: October 2012

This is a complex case of post-traumatic stress disorder (PTSD) with comorbid panic disorder occurring in a woman in her mid-60s, with a family history of neurotic illness. PTSD arose in the context of treatment for terminal lung cancer. This patient who had been close to her father watched him die of cancer, when he was about her age. Her diagnosis and treatment prompted traumatic recollections of her father's illness and death that resulted in her voluntary withdrawal from cancer treatment. The goals of treatment were to promptly reduce anxiety, minimise use of sedating pharmacotherapy, promote lucidity and prolong anxiety-free state thereby allowing time for important family interactions. Prompt, sustained relief of severe anxiety was necessary to achieve comfort at the end of life. Skilled additions of psychological therapies (eye movement desensitisation reprocessing, clinical hypnosis and breathing exercises) with combined pharmacotherapy (mirtazepine and quetiapine) led to control of anxiety and reduction of post-traumatic stress.
Caffey disease in neonatal period: the importance of the family!
Authors: Prior Ana Rita , Moldovan Oana , Azevedo António , Moniz Carlos
Published: October 2012

A male newborn was apparently well until his second day of life, when increased irritability and a swelling in his right leg were noted. He was rooming-in with his mother since birth. On examination, a mass on the anterior surface of the right leg was noticed. The mass was firm, elongated, ill-defined, unmovable and painful at palpation. No overlying skin changes were seen. The newborn had a family history of neonatal bone swelling with resolution before the age of 2. Subsequent images showed hyperostosis in the diaphysis of the right tibia. After exclusion of other conditions such as trauma, osteomyelitis and congenital syphilis, the involvement of the tibial diaphysis, sparing the epiphyses and the benign course of the disease in family history, were indicative of Caffey disease. The genetic study confirmed this diagnosis. Caffey disease, although rare, should not be overlooked in the diagnostic approach to childhood bone swelling.
Periampullary mass—a rare presentation of poorly differentiated neuroendocrine cancer of duodenum in a young adult: a case report and review of literature
Authors: Singh Neha , Nayak Hemanta K , Bagchi Avishek , Kar Premashis
Published: October 2012

Poorly differentiated neuroendocrine tumour in the periampullary region of the duodenum is a rare entity. This entity usually present in old men. Here we report a periampullary poorly differentiated neuroendocrine cancer (PDEC) of duodenum presenting in a young man with subacute history of jaundice, abdominal pain, pancreatitis and constitutional symptoms. MRI localised the tumour and endoscopy-guided biopsy of the lesion proved the diagnosis. Although palliative surgery and chemotherapy were planned, the patient opted to leave against medical advice.