bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical expenditures of adult cancer survivors aged <65 years in the United States
Authors: Short Pamela Farley , Moran John R. , Punekar Rajeshwari
Published: December 2010

BACKGROUND:

To the authors' knowledge, this is the first study to provide national estimates of medical expenditures for all adult cancer survivors aged <65 years. Most studies of expenditures for cancer survivors in this age group have been based on the Medical Expenditure Panel Survey (MEPS) and were limited to “affected survivors.”

METHODS:

MEPS expenditure data for 2001 to 2007 were linked to data identifying all survivors from the National Health Interview Survey (NHIS), which is the MEPS sampling frame. The sample was comprised of adults ages 25 to 64 years. Propensity‐score matching was used to estimate the effects of cancer on average total and out‐of‐pocket expenditures for all services and separately for prescriptions. Probit models were used to estimate effects on the probability of exceeding different expenditure thresholds.

RESULTS:

Mean annual expenditures on all services in 2007 were $16,910 ± $3911 for survivors who were newly diagnosed with cancer, $7992 ± $972 for survivors who had been diagnosed in previous years, and $3303 ± $103 for other adults. Fifty‐three percent of survivors were not identified in MEPS but only by linking to NHIS. Expenditures for all survivors averaged approximately $9300 compared with $13,600 for “affected survivors.” For previously diagnosed survivors, the increase in mean expenditures attributable to cancer was approximately $4000 to $5000 annually. On average, relatively little of the increase was paid out of pocket, but cancer nearly doubled the risk of high out‐of‐pocket expenditures.

CONCLUSIONS:

Previous MEPS analyses overstated average expenditures for all survivors. Nevertheless, the current results indicated that the increase in expenditures attributable to cancer is substantial, even for longer term survivors, and that cancer increases the relative risk of high out‐of‐pocket expenditures. Cancer 2011;. © 2010 American Cancer Society.
Neoplastic pulmonary cytology
Authors: Cohen Michael B. , Weydert Jamie A.
Published: December 2010

With the advent of newer, targeted therapies for lung cancer the role of the cytologist is also changing. More refined diagnoses are being demanded as well as information about the expression of specific aberrant proteins. Cytologists need to be cognizant of these changes and, in particular, that the generic diagnosis of nonsmall cell lung cancer is likely to need refinement for contemporary management.
Three‐dimensional synaptic ultrastructure in the dentate gyrus and hippocampal area CA3 in the Ts65Dn mouse model of down syndrome
Authors: Popov Victor I. , Kleschevnikov Alexander M. , Klimenko Oleg A. , Stewart Michael G. , Belichenko Pavel V.
Published: December 2010

Down syndrome (DS) results from trisomy of human chromosome 21. Ts65Dn mice are an established model for DS and show several phenotypes similar to those in people with DS. However, there is little data on the structural plasticity of synapses in the trisynaptic pathway in the hippocampus. Here we investigate 3D ultrastructure of synapses in the hippocampus of age‐matched control (2N) and Ts65Dn male mice. Serial ultrathin sections and 3D reconstructions characterize synapses in the middle molecular layer (MML) of dentate gyrus and in thorny excrescences (TEs) in proximal portions of apical dendrites of CA3 pyramidal neurons. 3D analysis of synapses shows phenotypes that distinguish Ts65Dn from 2N mice. For the MML, synapse density was reduced by 15% in Ts65Dn vs. 2N mice (P < 0.05). Comparative 3D analyses demonstrate a significant decrease in the number of thorns per TE in CA3 in Ts65Dn vs. 2N mice (by ≈45%, P = 0.01). Individual thorn volume was 3 times smaller in Ts65Dn vs. 2N mice (P = 0.02). A significant decrease in the number of thorn projections per TE in Ts65Dn vs. 2N mice was accompanied by a decrease of filopodium‐like protrusions on the surface of TEs (P = 0.02). However, the volume of postsynaptic densities in CA3 Ts65Dn and 2N mice was unchanged (P = 0.78). Our findings suggest that the high degree of plasticity of CA3 thorns may be connected with their filopodial origin. Alterations of 3D synaptic structure in Ts65Dn mice may further contribute to the diminished plasticity in DS. J. Comp. Neurol. 519:1338–1354, 2011. © 2010 Wiley‐Liss, Inc.
Calcium‐binding protein distributions and fiber connections of the nucleus accumbens in the pigeon (columba livia)
Authors: Husband Scott A. , Shimizu Toru
Published: December 2010

Until recently, the exact location of the avian nucleus accumbens within the basal forebrain had not been well established (Reiner et al. [2004] J Comp Neurol 473:377–414). While a number of previous studies have shown afferents and efferents of the presumptive “nucleus accumbens,” detailed and accurate connection patterns of this newly recognized area are still lacking. We set out to clarify these connections using small, localized injections of cholera toxin subunit B and biotinylated dextran amine directly into the nucleus. In order to increase the accuracy of tracer injections into target sites, we first conducted a systematic comparison of three calcium‐binding proteins, namely, parvalbumin, calretinin, and calbindin, to characterize the nucleus accumbens and ascertain its boundaries. The results showed that the avian and mammalian nucleus accumbens had remarkable hodological similarities, including the connections with the hippocampus, amygdala, ventral pallidum, lateral hypothalamus, and ventral tegmental area. However, the most significant aspect of the present study is that the avian nucleus accumbens had extensive reciprocal connections with medial pallial structures, the mammalian counterparts of which are unclear. Three implications of this finding are discussed. First, the avian medial pallium may correspond to part of the mammalian prefrontal cortex based on the connections with the nucleus accumbens. Second, the avian brain has a “limbic loop” involving the medial pallium, which also receives input from the avian equivalent of the mediodorsal thalamus. Third, the extensive connections between the accumbens and medial pallium just dorsal to it suggest a column‐like organization of limbic‐associated areas in the avian telencephalon. J. Comp. Neurol. 519:1371–1394, 2011. © 2010 Wiley‐Liss, Inc.
Synaptic proteins are tonotopically graded in postnatal and adult type I and type II spiral ganglion neurons
Authors: Flores‐Otero Jacqueline , Davis Robin L.
Published: December 2010

Inherent in the design of the mammalian auditory system is the precision necessary to transduce complex sounds and transmit the resulting electrical signals to higher neural centers. Unique specializations in the organ of Corti are required to make this conversion, such that mechanical and electrical properties of hair cell receptors are tailored to their specific role in signal coding. Electrophysiological and immunocytochemical characterizations have shown that this principle also applies to neurons of the spiral ganglion, as evidenced by distinctly different firing features and synaptic protein distributions of neurons that innervate high‐ and low‐frequency regions of the cochlea. However, understanding the fine structure of how these properties are distributed along the cochlear partition and within the type I and type II classes of spiral ganglion neurons is necessary to appreciate their functional significance fully. To address this issue, we assessed the localization of the postsynaptic AMPA receptor subunits GluR2 and GluR3 and the presynaptic protein synaptophysin by using immunocytochemical labeling in both postnatal and adult tissue. We report that these presynaptic and postsynaptic proteins are distributed oppositely in relation to the tonotopic map and that they are equally distributed in each neuronal class, thus having an overall gradation from one end of the cochlea to the other. For synaptophysin, an additional layer of heterogeneity was superimposed orthogonal to the tonotopic axis. The highest anti‐synaptophysin antibody levels were observed within neurons located close to the scala tympani compared with those located close to the scala vestibuli. Furthermore, we noted that the protein distribution patterns observed in postnatal preparations were largely retained in adult tissue sections, indicating that these features characterize spiral ganglion neurons in the fully developed ear. J. Comp. Neurol. 519:1455–1475, 2011. © 2010 Wiley‐Liss, Inc.
Neurogliaform cells in the molecular layer of the dentate gyrus as feed‐forward γ‐aminobutyric acidergic modulators of entorhinal–hippocampal interplay
Authors: Armstrong Caren , Szabadics János , Tamás Gábor , Soltesz Ivan
Published: December 2010

Feed‐forward inhibition from molecular layer interneurons onto granule cells (GCs) in the dentate gyrus is thought to have major effects regulating entorhinal–hippocampal interactions, but the precise identity, properties, and functional connectivity of the GABAergic cells in the molecular layer are not well understood. We used single and paired intracellular patch clamp recordings from post‐hoc‐identified cells in acute rat hippocampal slices and identified a subpopulation of molecular layer interneurons that expressed immunocytochemical markers present in members of the neurogliaform cell (NGFC) class. Single NGFCs displayed small dendritic trees, and their characteristically dense axonal arborizations covered significant portions of the outer and middle one‐thirds of the molecular layer, with frequent axonal projections across the fissure into the CA1 and subicular regions. Typical NGFCs exhibited a late firing pattern with a ramp in membrane potential prior to firing action potentials, and single spikes in NGFCs evoked biphasic, prolonged GABAA and GABAB postsynaptic responses in GCs. In addition to providing dendritic GABAergic inputs to GCs, NGFCs also formed chemical synapses and gap junctions with various molecular layer interneurons, including other NGFCs. NGFCs received low‐frequency spontaneous synaptic events, and stimulation of perforant path fibers revealed direct, facilitating synaptic inputs from the entorhinal cortex. Taken together, these results indicate that NGFCs form an integral part of the local molecular layer microcircuitry generating feed‐forward inhibition and provide a direct GABAergic pathway linking the dentate gyrus to the CA1 and subicular regions through the hippocampal fissure. J. Comp. Neurol. 519:1476–1491, 2011. © 2010 Wiley‐Liss, Inc.
Patterns of axonal collateralization of single layer V cortical projection neurons in the rat presubiculum
Authors: Honda Yoshiko , Furuta Takahiro , Kaneko Takeshi , Shibata Hideshi , Sasaki Hiroshi
Published: December 2010

The presubiculum is one of the important regions of the parahippocampal area known to be responsible for processing and integrating spatial representation information. To understand better the functional roles played by the presubiculum, it is essential to elucidate how output signals from the presubiculum distribute to its target regions. In the present study, the axonal branching patterns of single pyramidal neurons in layer V of the rat presubiculum were investigated by using in vivo injection of a viral vector expressing membrane‐targeted palmitoylation site‐attached green fluorescent protein. We found that individual layer V neurons provide axonal branches to one or two cortical areas with one or more recurrent collaterals to the presubiculum. These neurons were classified into six types, based on their axonal collateralization pattern: neurons with axon branches to 1) both the retrosplenial granular cortex and the parasubiculum, 2) both the retrosplenial granular cortex and the subiculum, and 3) both the medial entorhinal area and the subiculum, and neurons with axonal branches terminating only in 4) the retrosplenial granular cortex, 5) the subiculum, and 6) the presubiculum. Types 1–5 also provide recurrent axons to the presubiculum. Our data demonstrate that layer V of the presubiculum consists of at least six types of cortical projection neurons with various patterns of axonal collateralization. These findings suggest that single presubicular layer V neurons may distribute information to one or two cortical areas participating in the neural circuitry of spatial representation and also send such information back to the presubiculum itself. J. Comp. Neurol. 519:1395–1412, 2011. © 2010 Wiley‐Liss, Inc.
Structure and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse
Authors: Schmidt Tiffany M. , Kofuji Paulo
Published: December 2010

A subpopulation of retinal ganglion cells (RGCs) expresses the photopigment melanopsin, rendering these cells intrinsically photosensitive (ipRGCs). These cells are critical for competent circadian entrainment, pupillary light reflex, and other non‐imaging‐forming photic responses. Research has now demonstrated the presence of multiple subpopulations of ipRGC based on the dendritic stratification in the inner plexiform layer (IPL), those monostratified in the Off sublamina (M1), those monostratified in the On sublamina (M2,4,5), and those bistratified in both the On and the Off sublaminae (M3). Despite evidence that M1 and M2 cells are distinct subpopulations of ipRGC based on distinct morphological and physiological properties, the inclusion of M3 cells as a distinct subtype has remained controversial. Aside from the identification of M3 cells as a morphological subpopulation of ipRGC, to date there have been no functional descriptions of M3 cell physiology or synaptic inputs. Our data provide the first in‐depth description of M3 cell structural and functional properties. We report that M3 cells form a morphologically heterogeneous population but one that is physiologically homogeneous with properties similar to those of M2 cells. J. Comp. Neurol. 519:1492–1504, 2011. © 2010 Wiley‐Liss, Inc.
Brain‐derived neurotrophic factor promotes cochlear spiral ganglion cell survival and function in deafened, developing cats
Authors: Leake Patricia A. , Hradek Gary T. , Hetherington Alexander M. , Stakhovskaya Olga
Published: December 2010

Postnatal development and survival of spiral ganglion (SG) neurons depend on both neural activity and neurotrophic support. Our previous studies showed that electrical stimulation from a cochlear implant only partially prevents SG degeneration after early deafness. Thus, neurotrophic agents that might be combined with an implant to improve neural survival are of interest. Recent studies reporting that brain‐derived neurotrophic factor (BDNF) promotes SG survival after deafness have been conducted in rodents and limited to relatively short durations. Our study examined longer duration BDNF treatment in deafened cats that may better model the slow progression of SG degeneration in human cochleae, and this is the first study of BDNF in the developing auditory system. Kittens were deafened neonatally, implanted at 4–5 weeks with intracochlear electrodes containing a drug‐delivery cannula, and BDNF or artificial perilymph was infused for 10 weeks from a miniosmotic pump. In BDNF‐treated cochleae, SG cells grew to normal size and were significantly larger than cells on the contralateral side. However, their morphology was not completely normal, and many neurons lacked or had thinned perikaryl myelin. Unbiased stereology was employed to estimate SG cell density, independent of cell size. BDNF was effective in promoting significantly improved survival of SG neurons in these developing animals. BDNF treatment also resulted in higher density and larger size of myelinated radial nerve fibers, sprouting of fibers into the scala tympani, and improvement of electrically evoked auditory brainstem response thresholds. BDNF may have potential therapeutic value in the developing auditory system, but many serious obstacles currently preclude clinical application. J. Comp. Neurol. 519:1526–1545, 2011. © 2010 Wiley‐Liss, Inc.
A specific antibody to neuropeptide AF1 (KNEFIRFamide) recognizes a small subset of neurons in Ascaris suum: differences from Caenorhabditis elegans
Authors: Sithigorngul Paisarn , Jarecki Jessica L. , Stretton Antony O.W.
Published: December 2010

A monoclonal antibody, AF1‐003, highly specific to the Ascaris suum neuropeptide AF1 (KNEFIRFamide), was generated. This antibody binds strongly to AF1 and extremely weakly to other peptides with C‐terminal FIRFamide: AF5 (SGKPTFIRFamide), AF6 (FIRFamide), and AF7 (AGPRFIRFamide). It does not recognize 35 other AF (A. suum FMRFamide‐like) peptides at the highest concentration tested, nor does it recognize FMRFamide. When crude peptide extracts of A. suum are fractionated by two‐step HPLC, the only fractions recognized by AF1‐003 are those comigrating with synthetic AF1. By immunocytochemistry, antibody AF1‐003 recognizes a small subset of the 298 neurons of A. suum: these include the paired URX and RIP neurons, two pairs of lateral ganglion neurons in the head, and the unpaired PQR and PDA or ‐B tail neurons that send processes to the head along the dorsal and ventral nerve cords, respectively. AF1 immunoreactivity is also seen in three pairs of pharyngeal neurons. Mass spectroscopy (MS) shows the presence of AF1 in the head, pharynx, and dorsal and ventral nerve cords. In A. suum, the neurons that contain AF1 show little overlap with neurons that express green fluorescent protein constructs targeting the flp‐8 gene, which encodes AF1 in Caenorhabditis elegans (Kim and Li [2004] J. Comp. Neurol. 475:540–550); the URX neurons express AF1 in both species, but, in C. elegans, flp‐8 expression was not detected in RIP, PQR, and PDA or ‐B or in the pharynx. Other, less specific monoclonal antibodies recognize AF1, as well as other peptides to differing degrees; these antibodies are useful reagents for determination of neuronal morphology. J. Comp. Neurol. 519:1546–1561, 2011. © 2010 Wiley‐Liss, Inc.
Formation of the spinal network in zebrafish determined by domain‐specific pax genes
Authors: Ikenaga Takanori , Urban Jason M. , Gebhart Nichole , Hatta Kohei , Kawakami Koichi , Ono Fumihito
Published: December 2010

In the formation of the spinal network, various transcription factors interact to develop specific cell types. By using a gene trap technique, we established a stable line of zebrafish in which the red fluorescent protein (RFP) was inserted into the pax8 gene. RFP insertion marked putative pax8‐lineage cells with fluorescence and inhibited pax8 expression in homozygous embryos. Pax8 homozygous embryos displayed defects in the otic vesicle, as previously reported in studies with morpholinos. The pax8 homozygous embryos survived to adulthood, in contrast to mammalian counterparts that die prematurely. RFP is expressed in the dorsal spinal cord. Examination of the axon morphology revealed that RFP+ neurons include commissural bifurcating longitudinal (CoBL) interneurons, but other inhibitory neurons such as commissural local (CoLo) interneurons and circumferential ascending (CiA) interneurons do not express RFP. We examined the effect of inhibiting pax2a/pax8 expression on interneuron development. In pax8 homozygous fish, the RFP+ cells underwent differentiation similar to that of pax8 heterozygous fish, and the swimming behavior remained intact. In contrast, the RFP+ cells of pax2a/pax8 double mutants displayed altered cell fates. CoBLs were not observed. Instead, RFP+ cells exhibited axons descending ipsilaterally, a morphology resembling that of V2a/V2b interneurons. J. Comp. Neurol. 519:1562–1579, 2011. © 2010 Wiley‐Liss, Inc.
Synaptic inputs to two types of koniocellular pathway ganglion cells in marmoset retina
Authors: Percival Kumiko A. , Martin Paul R. , Grünert Ulrike
Published: December 2010

The retinal connectivity of the diverse group of cells contributing to koniocellular visual pathways (widefield ganglion cells) is largely unexplored. Here we examined the synaptic inputs onto two koniocellular‐projecting ganglion cell types named large sparse and broad thorny cells. Ganglion cells were labeled by retrograde tracer injections targeted to koniocellular layer K3 in the lateral geniculate nucleus in marmosets (Callithrix jacchus) and subsequently photofilled. Retinal preparations were processed with antibodies against the C‐terminal binding protein 2, the AMPA receptor subunit GluR4, and against CD15 to identify bipolar (excitatory) and/or antibodies against gephyrin to identify amacrine (inhibitory) input. Large sparse cells are narrowly stratified close to the ganglion cell layer. Broad thorny ganglion cells are broadly stratified in the center of the inner plexiform layer. Bipolar input to large sparse cells derives from DB6 and maybe other ON bipolar types, whereas that to broad thorny cells derives from ON and OFF bipolar cell types. The total number of putative synapses on broad thorny cells is higher than the number on large sparse cells but the density of inputs (between 2 and 5 synapses per 100 μm2 dendritic area) is similar for the two cell types, indicating that the larger number of synapses on broad thorny cells is attributable to the larger membrane surface area of this cell type. Synaptic input density is comparable to previous values for midget‐parvocellular and parasol‐magnocellular pathway cells. This suggests functional differences between koniocellular, parvocellular, and magnocellular pathways do not arise from variation in synaptic input densities. J. Comp. Neurol. 519:2135–2153, 2011. © 2010 Wiley‐Liss, Inc.
Major isoform of zebrafish P0 is a 23.5 kDa myelin glycoprotein expressed in selected white matter tracts of the central nervous system
Authors: Bai Qing , Sun Ming , Stolz Donna B. , Burton Edward A.
Published: December 2010

The zebrafish mpz gene, encoding the ortholog of mammalian myelin protein zero, is expressed in oligodendrocytes of the zebrafish central nervous system (CNS). The putative gene product, P0, has been implicated in promoting axonal regeneration in addition to its proposed structural functions in compact myelin. We raised novel zebrafish P0‐specific antibodies and established that P0 is a 23.5 kDa glycoprotein containing a 3 kDa N‐linked carbohydrate moiety. P0 was localized to myelin sheaths surrounding axons, but was not detected in the cell bodies or proximal processes of oligodendrocytes. Many white matter tracts in the adult zebrafish CNS were robustly immunoreactive for P0, including afferent visual and olfactory pathways, commissural and longitudinal tracts of the brain, and selected ascending and descending tracts of the spinal cord. P0 was first detected during development in premyelinating oligodendrocytes of the ventral hindbrain at 48 hours postfertilization (hpf). By 72 hpf, short segments of longitudinally oriented P0‐immunoreactive myelinating axons were seen in the hindbrain; expression in the spinal cord, optic pathways, hindbrain commissures, midbrain, and peripheral nervous system followed. The mpz transcript was found to be alternatively spliced, giving rise to P0 isoforms with alternative C‐termini. The 23.5 kDa isoform was most abundant in the CNS, but other isoforms predominated in the myelin sheath surrounding the Mauthner axon. These data provide a detailed account of P0 expression and demonstrate novel P0 isoforms, which may have discrete functional properties. The restriction of P0 immunoreactivity to myelin sheaths indicates that the protein is subject to stringent intracellular compartmentalization, which likely occurs through posttranslational mechanisms. J. Comp. Neurol. 519:1580–1596, 2011. © 2010 Wiley‐Liss, Inc.
Increase of close homolog of cell adhesion molecule L1 in primary afferent by nerve injury and the contribution to neuropathic pain
Authors: Yamanaka Hiroki , Kobayashi Kimiko , Okubo Masamichi , Fukuoka Tetsuo , Noguchi Koichi
Published: December 2010

The L1 family of cell adhesion molecules (L1‐CAMs) is known to be involved in various neuronal functions such as cell adhesion, axon guidance, and synaptic plasticity. We investigated the detailed expression/changes of a close homolog of the L1 cell adhesion molecule (CHL1) after nerve injury and the possible role on neuropathic pain using the rat spared nerve injury (SNI) model. SNI induced the expression of CHL1 in L4/5 DRG neurons, particularly in small‐size injured neurons and in satellite cells. In the spinal cord, CHL1 immunoreactivity increased mainly in laminae I–II of the dorsal horn on the side ipsilateral to the nerve injury. Ultrastructural study clarified the fine localization of CHL1 in axons of primary afferents in the dorsal horn. CHL1 immunoreactivities were localized in the adherence such as axon–axon, axon–dorsal horn neurons (dendrite, soma), and axon–glial cells (astrocyte and microglia). Experimental inhibition of CHL1 adhesion by intrathecal administration of the antibody for CHL1 extracellular domain significantly prevented and reversed SNI‐induced mechanical allodynia. Thus, alterations of CHL1 may be involved in the structural plasticity after peripheral nerve injury and have important roles in neuropathic pain. J. Comp. Neurol. 519:1597–1615, 2011. © 2010 Wiley‐Liss, Inc.
Mutually exclusive expression of Gαia and Gα14 reveals diversification of taste receptor cells in zebrafish
Authors: Ohmoto Makoto , Okada Shinji , Nakamura Shugo , Abe Keiko , Matsumoto Ichiro
Published: December 2010

A comprehensive reevaluation of the G protein alpha subunit genes specifically expressed in taste buds in the tongue epithelium of rodents revealed that Gq and G14 of the Gq class and Gi2 and Ggust (Gt3, also known as gustducin) of the Gi class are expressed in mammalian taste buds. Meanwhile, a database search of fish genomes revealed the absence of a gene encoding an ortholog of the mammalian Ggust gene, which mediates sweet, umami, and bitter taste signals in mammalian taste receptor cells (TRCs). Histochemical screening identified two G protein alpha subunit genes, zfGia and zfG14, expressed in subsets of TRCs in zebrafish. The expression patterns of zfGia and zfG14 in taste buds were mutually exclusive, and the expression of known T1R and T2R genes in zebrafish was restricted to a subset of zfGia‐expressing TRCs. These findings highlight the existence of a novel subset of TRCs in zebrafish that is absent in mammals and suggest that unidentified G protein‐coupled receptors are expressed in zfG14‐expressing TRCs and in zfGia‐expressing TRCs where known T1R and T2R genes were not expressed in zebrafish. The existence of not only generalized but also specialized subsets of TRCs may imply a strong connection between the evolution of the peripheral gustatory system and the evolution of particular species. J. Comp. Neurol. 519:1616–1629, 2011. © 2010 Wiley‐Liss, Inc.
Is gene duplication a viable explanation for the origination of biological information and complexity?
Authors: Bozorgmehr Joseph Esfandiar Hannon
Published: December 2010

All life depends on the biological information encoded in DNA with which to synthesize and regulate various peptide sequences required by an organism's cells. Hence, an evolutionary model accounting for the diversity of life needs to demonstrate how novel exonic regions that code for distinctly different functions can emerge. Natural selection tends to conserve the basic functionality, sequence, and size of genes and, although beneficial and adaptive changes are possible, these serve only to improve or adjust the existing type. However, gene duplication allows for a respite in selection and so can provide a molecular substrate for the development of biochemical innovation. Reference is made here to several well‐known examples of gene duplication, and the major means of resulting evolutionary divergence, to examine the plausibility of this assumption. The totality of the evidence reveals that, although duplication can and does facilitate important adaptations by tinkering with existing compounds, molecular evolution is nonetheless constrained in each and every case. Therefore, although the process of gene duplication and subsequent random mutation has certainly contributed to the size and diversity of the genome, it is alone insufficient in explaining the origination of the highly complex information pertinent to the essential functioning of living organisms. © 2011 Wiley Periodicals, Inc. Complexity, 2011
[70]Fullerene‐Based Materials for Organic Solar Cells
Authors: Troshin Pavel A. , Hoppe Harald , Peregudov Alexander S. , Egginger Martin , Shokhovets Sviatoslav , Gobsch Gerhard , Sariciftci N. Serdar , Razumov Vladimir F.
Published: December 2010

The synthesis, characterization and photovoltaic study of two novel derivatives of [70]fullerene, phenyl‐C71‐propionic acid propyl ester ([70]PCPP) and phenyl‐C71‐propionic acid butyl ester ([70]PCPB), are reported. [70]PCPP and [70]PCPB outperform the conventional material (6,6)‐phenyl‐C71‐butyric acid methyl ester ([70]PCBM) in solar cells based on poly(2‐methoxy‐5‐{3′,7′‐dimethyloctyloxy}‐p‐phenylene vinylene) (MDMO‐PPV) as a donor polymer using chlorobenzene (CB) or dichlorobenzene (DCB) as solvents. AFM data suggest that improvement of the device efficiency should be attributed to the increased phase compatibility between the novel C70 derivatives and the polymer matrix. [70]PCPP and [70]PCBM showed more or less equally high performances in solar cells comprising poly(3‐hexylthiophene) (P3HT) as a donor polymer. Optical modeling revealed that the application of [70]fullerene derivatives as acceptor materials in P3HT‐based bulk heterojunction solar cells might give approximately 10 % higher short circuit current densities than using C60‐based materials such as [60]PCBM. The high solubility of [70]PCPP and [70]PCPB and their good compatibility with the donor polymers suggest these fullerene derivatives as promising electron acceptor materials for use in efficient bulk heterojunction organic solar cells.
Cross‐layer MAC design for location‐aware wireless sensor networks
Authors: Shi Qiong , Comaniciu Cristina , Wang Dandan , Tureli Ufuk
Published: December 2010

In this paper, we propose an optimization of MAC protocol design for wireless sensor networks, that accounts for cross‐layering information, in terms of location accuracy for nodes and residual energy levels. In our proposed solution we encode this cross‐layer information within a decreasing backoff function in the MAC. The protocol is optimized by appropriately selecting priority window lengths, and we have shown that accurate cross‐layer information plays a crucial role in achieving an optimal performance at the MAC layer level.

The estimation accuracy can be characterized spatially using a location reliability probability distribution function. We show that this distribution function greatly influences the design of the optimal backoff window parameters, and the overall throughput performance of the MAC protocol. Copyright © 2010 John Wiley & Sons, Ltd.
Applying in silico tools to the discovery of novel CXCR4 inhibitors
Authors: Pérez‐Nueno Violeta I. , Ritchie David W.
Published: December 2010

The process of HIV entry begins with the binding of the viral envelope glycoprotein gp120 to both the CD4 receptor and one of the CXCR4 or CCR5 chemokine co‐receptors. There is currently considerable interest in developing novel ligands that can bind to these co‐receptors and hence block virus‐cell fusion. This article reviews the use of different in silico structure‐based and ligand‐based virtual screening (VS) tools for the discovery of potential HIV entry inhibitors for the CXCR4 receptor. More specifically, it discusses homology modelling, de novo design, docking, QSAR analyses, pharmacophore modelling, and similarity searches. Results from retrospective VS of a library of known CXCR4 inhibitors taken from the literature and from prospective VS of a combinatorial virtual library are reviewed. The structures of active compounds found by these approaches, as well as CXCR4 inhibitors currently in development, are also discussed. Drug Dev Res 72: 95–111, 2011. © 2010 Wiley‐Liss, Inc.
The effect of combined CJZ3, a lomerizine derivative, with verapamil on P‐glycoprotein efflux function in vitro
Authors: Ji Bian‐Sheng , Ren Yan‐Li , He Ling
Published: December 2010

In the effort to inhibit P‐glycoprotein (P‐gp) efflux function with greater activity and less side effect, the combined effect of pair CJZ3 and verapamil (Ver) was evaluated isobolographically in numerous fixed‐ratio combinations of 1:1, 1:2, 1:4, 1:8, 1:10 in doxorubicin‐resistant human myelogenous leukemia (K562/ DOX) cells and in rat brain microvessel endothelial cells (RBMEC). The results displayed that mixtures of both drugs at the fixed‐ratios of 1:2, 1:4, 1:8, 1:10 exerted synergistic interactions, indicating that when the two reversers that bind P‐gp on separated sites were combined, each can contribute to the overall interaction with P‐gp, leading to the greater effect than that given by either agent alone. Drug Dev Res 72: 305–309, 2011.  © 2010 Wiley‐Liss, Inc.
The Cochrane Library and the treatment of croup in children: an overview of reviews
Authors: Bjornson Candice , Russell Kelly , Foisy Michelle , Johnson David W.
Published: December 2010

Background

Croup is an illness characterized by barky cough, stridor, hoarseness, and occasionally respiratory distress. It is a relatively mild and short‐lived illness for the majority of children. However, a small proportion of children have moderate to severe symptoms and are at risk of hospital admission, and in the most severe cases, intubation.

Objective

To synthesize the evidence currently in The Cochrane Database of Systematic Reviews (CDSR) related to the clinical effectiveness and applicability of four treatments for croup: glucocorticoids, epinephrine, heliox and humidified air.

Methods

The CDSR was searched for all systematic reviews containing the term ‘croup’ in the title. Pharmacologic and nonpharmacologic interventions for the treatment of croup in children were included. Data were extracted, compiled into tables and synthesized using qualitative and quantitative methods.

Main Results

Four reviews examining the treatment of croup were included in this overview. Children treated with epinephrine vs placebo had a significantly lower croup score at 30 min (SMD: − 0.94; 95% CI: − 1.37, − 0.51), and children treated with glucocorticoids vs placebo had significantly lower croup scores at both 6 h and 12 h (SMD: − 0.59; 95% CI: − 0.83, − 0.35 and SMD: − 0.65; 95% CI: − 1.03, − 0.27). Glucocorticoids vs placebo also significantly reduced inpatient length of stay (MD: − 10.33; 95% CI: − 17.33, − 3.36) and risk of return visits and/or re‐admissions (RR: 0.49; 95% CI: 0.34, 0.71). Neither humidified air nor heliox were associated with significant reductions in croup score; however, there is a paucity of evidence examining treatment with heliox.

Author's Conclusions

Glucocorticoids are effective for children with mild croup, and both nebulized epinephrine and glucocorticoids are effective treatments for children presenting with moderate to severe croup that is associated with respiratory distress. There is insufficient evidence to determine the effectiveness of heliox, and there is sufficient evidence to suggest that humidified air is not effective in the treatment of croup. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Polymer‐based oral rehydration solution for treating acute watery diarrhoea’
Authors: Office Evidence‐Based Child Health Canadian Editorial
Published: December 2010

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Gregorio GV, Gonzales MLM, Dans LF, Martinez EG. Polymer‐based oral rehydration solution for treating acute watery diarrhoea. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD006519. DOI: 10.1002/14651858.CD006519.pub2. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Braces for idiopathic scoliosis in adolescents’
Authors: Office Evidence‐Based Child Health Canadian Editorial
Published: December 2010

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Negrini S, Minozzi S, Bettany‐Saltikov J, Zaina F, Chockalingam N, Grivas TB, Kotwicki T, Maruyama T, Romano M, Vasiliadis ES. Braces for idiopathic scoliosis in adolescents. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD006850. DOI: 10.1002/14651858.CD006850.pub2. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus’
Authors: Office Evidence‐Based Child Health Canadian Editorial
Published: December 2010

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Misso ML, Egberts KJ, Page M, O'Connor D, Shaw J. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD005103. DOI: 10.1002/14651858.CD005103.pub2. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Conventional occlusion versus pharmacologic penalization for amblyopia’
Authors: Office Evidence‐Based Child Health Canadian Editorial
Published: December 2010

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Li T, Shotton K. Conventional occlusion versus pharmacologic penalization for amblyopia. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD006460. DOI: 10.1002/14651858.CD006460.pub2. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentaries on ‘Conventional occlusion versus pharmacological penalization for amblyopia’
Authors: Sloper John J. , Tejedor Jaime
Published: December 2010

These are commentaries on a Cochrane review, published in this issue of EBCH, first published as: Li T, Shotton K. Conventional occlusion versus pharmacologic penalization for amblyopia. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD006460. DOI: 10.1002/14 651 858.CD006460.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Chronic cough: a natural (and parental) disaster
Authors: Moja Lorenzo
Published: December 2010

These are the answers to the Dr Cochrane vignette on pages 1552–1554. How did you get on? Register your score at ebch@wiley.com Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
A transitional region concept for assessing the effects of reservoirs on river habitats: a case of Yangtze River, China
Authors: Wang Yuankun , Xia Ziqiang , Wang Dong
Published: December 2010

Dam constructions negatively impact river ecosystems by altering hydrologic regimes and connectivities. River continuum theory provides a useful framework for considering the specific influences of dams on the ecohydrology of river systems. This study presents a Transitional Region Concept for analysing the nature of hydrologic changes resulting from dam constructions and how these changes relate to the life history and ecology of the fish. The stream ecosystem of the transitional region is subdivided into a four‐dimensional framework. The framework consists of spatial structure, matter structure, energy structure, and hydrological process. The characteristics and variations in this framework, as affected by dam construction on the Yangtze River, are quantitatively assessed. The spawning ground of the Chinese Sturgeon (Acipenser sinensis), located in inertial zone of the river ecosystem, is used as the study site. Current and historical hydrological data are used to determine the effects of dam construction on the spawning grounds of Chinese Sturgeon in the river. The results show that the Three Gorges Reservoir (TGR) has a significant impact on the suitability of the spawning grounds of Chinese Sturgeon. This could also affect the prey/predator species dynamics and the sturgeon fish population in especially the lower reaches of the Yangtze River. The findings of this study could provide critical considerations for policy makers and river managers to protect Chinese Sturgeon from the adverse effects of the TGR. Copyright © 2010 John Wiley & Sons, Ltd.
A20 deficiency in B cells enhances B‐cell proliferation and results in the development of autoantibodies
Authors: Hövelmeyer Nadine , Reissig Sonja , Thi Xuan Nguyen , Adams‐Quack Petra , Lukas Dominika , Nikolaev Alexei , Schlüter Dirk , Waisman Ari
Published: December 2010

A20/TNFAIP3 is an ubiquitin‐editing enzyme, important for the regulation of the NF‐κB pathway. Mutations in the TNFAIP3 gene have been linked to different human autoimmune disorders. In human B‐cell lymphomas, the inactivation of A20 results in constitutive NF‐κB activation. Recent studies demonstrate that in mice the germline inactivation of A20 leads to early lethality, due to inflammation in multiple organs of the body. In this report, we describe a new mouse strain allowing for the tissue‐specific deletion of A20. We show that B‐cell‐specific deletion of A20 results in a dramatic reduction in marginal zone B cells. Furthermore, A20‐deficient B cells display a hyperactive phenotype represented by enhanced proliferation upon activation. Finally, these mice develop higher levels of serum immunoglobulins, resulting in an excessive production of self‐reactive autoantibodies.
Water Adsorption Characteristics of MIL‐101 for Heat‐Transformation Applications of MOFs
Authors: Ehrenmann Johannes , Henninger Stefan K. , Janiak Christoph
Published: December 2010

The adsorption of water vapor in the highly porous metal‐organic framework (MOF) of 3D‐[Cr3F(H2O)2O(bdc)3·~25H2O] (MIL‐101) (bdc = benzene‐1,4‐dicarboxylate, terephthalate) of up to 1 g of water per gram of sorbent material (between 140 °C and 40 °C under a water vapor pressure of 5.6 kPa) together with the stability over several cycles makes MIL‐101 the most promising material, so far, for heat transformation applications like thermally driven heat pumps or adsorption chillers.
Two Coordination Polymers with Rare Topologies Based on Copper(II) and Ligands Generated by In Situ Reactions (Eur. J. Inorg. Chem. 1/2011)
Authors: Li Baiyan , Jin Di , Ma Benhua , Liu Dan , Li Guanghua , Shi Zhan , Feng Shouhua
Published: December 2010

The cover picture shows that two coordination polymers exhibiting rare NiP2 topology and kgd topology are constructed on the basis of Cu2+ and ligands 3,5‐bipyridyl‐1,2,4‐triazole and 5‐(3‐pyridyl)‐1,2,4‐triazolo[3,2‐c](7‐aza‐1H‐indazole) formed through in situ ligand deaminization and in situ ligand intramolecular amination cyclization reactions. Details are discussed in the Short Communication by Z. Shi et al. on p. 35 ff. Dedicated to Professors Ruren Xu and Wenqin Pang on the occasion of their 80th birthdays, with our warmest congratulations and best wishes.
Diastereospecific Coupling of Imines by Low‐Valent Titanium: An Experimental and Computational Study
Authors: Kumar Akshai , Samuelson Ashoka G.
Published: December 2010

The reaction of phenylsilane (PhSiH3) and titanium(IV) isopropoxide [Ti(OiPr)4] generates low‐valent titanium alkoxides that reduce and reductively couple imines. The C–C coupling reaction is diastereospecific, with exclusive formation of the (±)‐isomer. The yield is dependent on the concentration of titanium(IV) isopropoxide used. Using imines with varying electronic demand revealed that the coupling is most efficient for unsubstituted imines. The involvement of a trimeric titanium biradical species is invoked to explain the observed concentration dependence and diastereospecificity in the reaction. Multilayer ONIOM (“our own n‐layered integrated molecular orbital and molecular mechanics”) calculations were carried out on the plausible intermediates involved by using the Guassian 09 suite of programs. Formation of the trimeric biradical species leading to the formation of the (±)‐isomer is more favored than formation of the trimeric biradical species, which leads to the meso‐isomer. Similar calculations with dimeric intermediates do not predict the (±)‐selectivity. Mass spectral analysis of the reaction mixture indicates the presence of a trimeric titanium alkoxide species.
Mucin (MUC5AC) expression by lung epithelial cells cultured in a microfluidic gradient device
Authors: Kim Su Hwan , Kang Jin Hyun , Chung Il Yup , Chung Bong Geun
Published: December 2010

We have developed a microfluidic gradient device for controlling mucin gene expression of NCI‐H292 epithelial cells derived from lung tissues. We hypothesized that gradient profiles would control mucin gene expression of lung epithelial cells. However, it was not possible to generate various stable gradient profiles using conventional culture methods. To address this limitation, we used a microfluidic gradient device to create various gradient profiles (i.e. non‐linear, linear, and flat) in a temporal and spatial manner. NCI‐H292 lung epithelial cells were exposed to concentration gradients of epidermal growth factor in a microfluidic gradient device with continuous medium perfusion. We demonstrated an effect of gradient profiles on mucin expression of lung epithelial cells cultured in the microfluidic gradient device. It was revealed that NCI‐H292 lung epithelial cells exposed to the flat gradient profile of the epidermal growth factor exhibited high expression of mucin as compared with cells exposed to non‐linear and linear gradient profiles. Therefore, this microfluidic gradient device could be a potentially useful tool for regulating the mucin expression of lung epithelial cells exposed to chemokine gradient profiles.
Identification of mutagens in freshwater sediments by the Ames‐fluctuation assay using nitroreductase and acetyltransferase overproducing test strains
Authors: Reifferscheid Georg , Buchinger Sebastian , Cao Zhi , Claus Evelyn
Published: December 2010

Extracts of sediments from an area of concern in the Elbe river basins (Spittelwasser creek) were analyzed with the Ames‐fluctuation test and in parallel with gas chromatography/mass spectrometry for compound identification. The standard test strains TA 98 and TA 100 showed mutagenicity mainly in medium‐polar fractions of the sediment extracts. PAHs contribute to the overall mutagenic potential of the sample. Especially, cyclopenta[c,d]pyrene that was previously not defined as a priority hazardous substance has to be considered as well. The addition of metabolically competent test strains, which overexpress nitroreductase and acetyltransferase (e.g., YG1041 and YG1042) to the test battery, increased significantly the sensitivity of the Ames test for medium polar to polar genotoxins. The increased mutagenicity that was found in these bacterial strains indicates the presence of nitroarenes and/or aromatic amines. In fact, a number of heterocyclic and nitrogen‐substituted aromatic compounds were identified in the sediments of the Spittelwasser creek of which methyl parathion, 1‐naphthylamine, and N‐phenyl‐2‐naphthylamine are mutagenic. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.