bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidimensional wave field signal theory: Mathematical foundations
Authors: Baddour Natalie
Published: May 2011

Many important physical phenomena are described by wave or diffusion-wave type equations. Since these equations are linear, it would be useful to be able to use tools from the theory of linear signals and systems in solving related forward or inverse problems. In particular, the transform domain signal description from linear system theory has shown concrete promise for the solution of problems that are governed by a multidimensional wave field. The aim is to develop a unified framework for the description of wavefields via multidimensional signals. However, certain preliminary mathematical results are crucial for the development of this framework. This first paper on this topic thus introduces the mathematical foundations and proves some important mathematical results. The foundation of the framework starts with the inhomogeneous Helmholtz or pseudo-Helmholtz equation, which is the mathematical basis of a large class of wavefields. Application of the appropriate multi-dimensional Fourier transform leads to a transfer function description. To return to the physical spatial domain, certain mathematical results are necessary and these are presented and proved here as six fundamental theorems. These theorems are crucial for the evaluation of a certain class of improper integrals which arise in the evaluation of inverse multi-dimensional Fourier and Hankel transforms, upon which the framework is based. Subsequently, applications of these theorems are demonstrated, in particular for the derivation of Green's functions in different coordinate systems.
Stereoscopic full aperture imaging in nuclear medicine
Authors: Strocovsky Sergio G. , Otero Dino
Published: May 2011

Images of planar scintigraphy and single photon emission computerized tomography (SPECT) used in nuclear medicine are often low quality. They usually appear to be blurred and noisy. This problem is due to the low spatial resolution and poor sensitivity of the acquisition technique with the gamma camera (GC). Other techniques, such as coded aperture imaging (CAI) reach higher spatial resolutions than GC. However, CAI is not frequently used for imaging in nuclear medicine, due to the decoding complexity of some images and the difficulty in controlling the noise magnitude. Summing up, the images obtained through GC are low quality and it is still difficult to implement CAI technique. A novel technique, full aperture Imaging (FAI), also uses gamma ray-encoding to obtain images, but the coding system and the method of images reconstruction are simpler than those used in CAI. In addition, FAI also reaches higher spatial resolution than GC. In this work, the principles of FAI technique and the method of images reconstruction are explained in detail. The FAI technique is tested by means of Monte Carlo simulations with filiform and spherical sources. Spatial resolution tests of GC versus FAI were performed using two different source-detector distances. First, simulations were made without interposing any material between the sources and the detector. Then, other more realistic simulations were made. In these, the sources were placed in the centre of a rectangular prismatic region, filled with water. A rigorous comparison was made between GC and FAI images of the linear filiform sources, by means of two methods: mean fluence profile graphs and correlation tests. Finally, three-dimensional capacity of FAI was tested with two spherical sources. The results show that FAI technique has greater sensitivity (>100 times) and greater spatial resolution (>2.6 times) than that of GC with LEHR collimator, in both cases, with and without attenuating material and long and short-distance configurations. The FAI decoding algorithm reconstructs simultaneously four different projections which are located in separate image fields on the detector plane, while GC produces only one projection per acquisition. Simulations have allowed comparison of both techniques under ideal identical conditions. Our results show it is possible to apply an extremely simple encoded imaging technique, and get three-dimensional radioactivity information for simplistic geometry sources. The results are promising enough to evaluate the possibility of future research with more complex sources typical of nuclear medicine imaging.
An Activity-Based Cellular Automaton Model to Simulate Land-Use Dynamics
Authors: van Vliet Jasper , Hurkens Jelle , White Roger , van Delden Hedwig
Published: May 2011

In recent decades several methods have been proposed to simulate land-use changes in a spatially explicit way. In these models land is generally represented on a lattice with cell states indicating the predominant land use. Since a cell can have only one state, mixed land uses and different densities of one land use can only be introduced superficially, as separate cell states. In this paper we describe a cellular automata model that simulates dynamics in both land uses and activities, where activities represent quantitative information, such as the number of inhabitants at a location. Therefore each cell has associated with it (1) a value representing one of a finite set of land-use classes, and (2) a vector of numerical values representing the quantity of each modelled activity that is present at that location. This allows simulation of incremental changes as well as mixed land uses. The proposed model is tested with a synthetic application that uses two activities: population and jobs. It simulates the emergence of human settlements over time from local interactions between activities and land uses. Assessment of results indicates that the model generates realistic urbanization patterns.
Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs
Authors: Choi Kyung-Suk , Harfe Brian D.
Published: May 2011

The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a “wrapper” around the notochord to constrain these cells along the vertebral column.
Human telomerase model shows the role of the TEN domain in advancing the double helix for the next polymerization step
Authors: Steczkiewicz Kamil , Zimmermann Michael T. , Kurcinski Mateusz , Lewis Benjamin A. , Dobbs Drena , Kloczkowski Andrzej , Jernigan Robert L. , Kolinski Andrzej , Ginalski Krzysztof
Published: May 2011

Telomerases constitute a group of specialized ribonucleoprotein enzymes that remediate chromosomal shrinkage resulting from the “end-replication” problem. Defects in telomere length regulation are associated with several diseases as well as with aging and cancer. Despite significant progress in understanding the roles of telomerase, the complete structure of the human telomerase enzyme bound to telomeric DNA remains elusive, with the detailed molecular mechanism of telomere elongation still unknown. By application of computational methods for distant homology detection, comparative modeling, and molecular docking, guided by available experimental data, we have generated a three-dimensional structural model of a partial telomerase elongation complex composed of three essential protein domains bound to a single-stranded telomeric DNA sequence in the form of a heteroduplex with the template region of the human RNA subunit, TER. This model provides a structural mechanism for the processivity of telomerase and offers new insights into elongation. We conclude that the RNA∶DNA heteroduplex is constrained by the telomerase TEN domain through repeated extension cycles and that the TEN domain controls the process by moving the template ahead one base at a time by translation and rotation of the double helix. The RNA region directly following the template can bind complementarily to the newly synthesized telomeric DNA, while the template itself is reused in the telomerase active site during the next reaction cycle. This first structural model of the human telomerase enzyme provides many details of the molecular mechanism of telomerase and immediately provides an important target for rational drug design.
Flexible intuitions of Euclidean geometry in an Amazonian indigene group
Authors: Izard Véronique , Pica Pierre , Spelke Elizabeth S. , Dehaene Stanislas
Published: May 2011

Kant argued that Euclidean geometry is synthesized on the basis of an a priori intuition of space. This proposal inspired much behavioral research probing whether spatial navigation in humans and animals conforms to the predictions of Euclidean geometry. However, Euclidean geometry also includes concepts that transcend the perceptible, such as objects that are infinitely small or infinitely large, or statements of necessity and impossibility. We tested the hypothesis that certain aspects of nonperceptible Euclidian geometry map onto intuitions of space that are present in all humans, even in the absence of formal mathematical education. Our tests probed intuitions of points, lines, and surfaces in participants from an indigene group in the Amazon, the Mundurucu, as well as adults and age-matched children controls from the United States and France and younger US children without education in geometry. The responses of Mundurucu adults and children converged with that of mathematically educated adults and children and revealed an intuitive understanding of essential properties of Euclidean geometry. For instance, on a surface described to them as perfectly planar, the Mundurucu's estimations of the internal angles of triangles added up to ∼180 degrees, and when asked explicitly, they stated that there exists one single parallel line to any given line through a given point. These intuitions were also partially in place in the group of younger US participants. We conclude that, during childhood, humans develop geometrical intuitions that spontaneously accord with the principles of Euclidean geometry, even in the absence of training in mathematics.
Selectivity of terrestrial gastropod extinctions on an oceanic archipelago and insights into the anthropogenic extinction process
Authors: Chiba Satoshi , Roy Kaustuv
Published: May 2011

Anthropogenic impacts have led to widespread extinctions of species on oceanic islands but the nature of many of these extinctions remains poorly known. Here we investigate extinction selectivities of terrestrial gastropods from the Ogasawara archipelago in the northwest Pacific, where anthropogenic threats have changed over time, shifting primarily from the effects of habitat loss to predation by a variety of different predators. Across all of the islands, extinct species had significantly smaller geographic ranges compared with species that are still alive, but among the surviving species, ranges of those that are currently declining due to human impacts do not differ significantly from those that are not threatened. Extinctions were selective with respect to spire index (SI) of shells, a trait of potential functional importance, but the relationship between body size and extinction vulnerability varied among extinction agents, some of which were strongly size selective, whereas others were not. Overall, whereas anthropogenic impacts have resulted in nonrandom losses of phenotypic diversity, the patterns of selectivity are complex, vary among islands, and with the type of threat. As extinction agents have changed historically, so has the pattern of loss. Because of the changing nature of anthropogenic impacts, resiliency to one type of threat does not guarantee long-term survival of species and future patterns of biodiversity loss on these islands are likely to be different from those in the past
.
Infection with a plant virus modifies vector feeding behavior
Authors: Stafford Candice A. , Walker Gregory P. , Ullman Diane E.
Published: May 2011

Vector infection by some animal-infecting parasites results in altered feeding that enhances transmission. Modification of vector behavior is of broad adaptive significance, as parasite fitness relies on passage to a new host, and vector feeding is nearly always essential for transmission. Although several plant viruses infect their insect vectors, we have shown that vector infection by a plant virus alters feeding behavior. Here we show that infection withTomato spotted wilt virus(TSWV), type member of the only plant-infecting genus in theBunyaviridae, alters the feeding behavior of its thrips vector,Frankliniella occidentalis(Pergande). Male thrips infected with TSWV fed more than uninfected males, with the frequency of all feeding behaviors increasing by up to threefold, thus increasing the probability of virus inoculation. Importantly, infected males made almost three times more noningestion probes (probes in which they salivate, but leave cells largely undamaged) compared with uninfected males. A functional cell is requisite for TSWV infection and cell-to-cell movement; thus, this behavior is most likely to establish virus infection. Some animal-infecting members of theBunyaviridae(La Crosse virusandRift Valley fever virus) also cause increased biting rates in infected vectors. Concomitantly, these data support the hypothesis that capacity to modify vector feeding behavior is a conserved trait among plant- and animal-infecting members of theBunyaviridaethat evolved as a mechanism to enhance virus transmission. Our results underscore the evolutionary importance of vector behavioral modification to diverse parasites with host ranges spanning both plant and animal kingdoms.
Convergent transcription confers a bistable switch in
Enterococcus faecalis
conjugation
Authors: Chatterjee Anushree , Johnson Christopher M. , Shu Che-Chi , Kaznessis Yiannis N. , Ramkrishna Doraiswami , Dunny Gary M. , Hu Wei-Shou
Published: May 2011

Convergent gene pairs with head-to-head configurations are widespread in both eukaryotic and prokaryotic genomes and are speculated to be involved in gene regulation. Here we present a unique mechanism of gene regulation due to convergent transcription from the antagonistic
prgX/prgQ
operon in
Enterococcus faecalis
controlling conjugative transfer of the antibiotic resistance plasmid pCF10 from donor cells to recipient cells. Using mathematical modeling and experimentation, we demonstrate that convergent transcription in the
prgX/prgQ
operon endows the system with the properties of a robust genetic switch through premature termination of elongating transcripts due to collisions between RNA polymerases (RNAPs) transcribing from opposite directions and antisense regulation between complementary counter-transcripts. Evidence is provided for the presence of truncated RNAs resulting from convergent transcription from both the promoters that are capable of sense–antisense interactions. A mathematical model predicts that both RNAP collision and antisense regulation are essential for a robust bistable switch behavior in the control of conjugation initiation by
prgX/prgQ
operons. Moreover, given that convergent transcription is conserved across species, the mechanism of coupling RNAP collision and antisense interaction is likely to have a significant regulatory role in gene expression.
Guanine nucleotide exchange factor Vav1 regulates perivascular homing and bone marrow retention of hematopoietic stem and progenitor cells
Authors: Sanchez-Aguilera Abel , Lee Yun-Jung , Lo Celso Cristina , Ferraro Francesca , Brumme Kristina , Mondal Subhanjan , Kim Chaekyun , Dorrance Adrienne , Luo Hongbo R. , Scadden David T. , Williams David A.
Published: May 2011

Engraftment and maintenance of hematopoietic stem and progenitor cells (HSPC) depend on their ability to respond to extracellular signals from the bone marrow microenvironment, but the critical intracellular pathways integrating these signals remain poorly understood. Furthermore, recent studies provide contradictory evidence of the roles of vascular versus osteoblastic niche components in HSPC function. To address these questions and to dissect the complex upstream regulation of Rac GTPase activity in HSPC, we investigated the role of the hematopoietic-specific guanine nucleotide exchange factor Vav1 in HSPC localization and engraftment. Using intravital microscopy assays, we demonstrated that transplanted

Vav1
−/−

HSPC showed impaired early localization near nestin
+
perivascular mesenchymal stem cells; only 6.25% of

Vav1
−/−

HSPC versus 45.8% of wild-type HSPC were located less than 30 μm from a nestin
+
cell. Abnormal perivascular localization correlated with decreased retention of

Vav1
−/−

HSPC in the bone marrow (44–60% reduction at 48 h posttransplant, compared with wild-type) and a very significant defect in short- and long-term engraftment in competitive and noncompetitive repopulation assays (<1.5% chimerism of

Vav1
−/−

cells vs. 53–63% for wild-type cells). The engraftment defect of

Vav1
−/−

HSPC was not related to alterations in proliferation, survival, or integrin-mediated adhesion. However,

Vav1
−/−

HSPC showed impaired responses to SDF1α, including reduced in vitro migration in time-lapse microscopy assays, decreased circadian and pharmacologically induced mobilization in vivo, and dysregulated Rac/Cdc42 activation. These data suggest that Vav1 activity is required specifically for SDF1α-dependent perivascular homing of HSPC and suggest a critical role for this localization in retention and subsequent engraftment.
The DISABLED protein functions in CLATHRIN-mediated synaptic vesicle endocytosis and exoendocytic coupling at the active zone
Authors: Kawasaki Fumiko , Iyer Janani , Posey Lisa L. , Sun Chichun E. , Mammen Samantha E. , Yan Huaru , Ordway Richard W.
Published: May 2011

Members of the DISABLED (DAB) family of proteins are known to play a conserved role in endocytic trafficking of cell surface receptors by functioning as monomeric CLATHRIN-associated sorting proteins that recruit cargo proteins into endocytic vesicles. Here, we report a
Drosophila disabled
mutant revealing a novel role for DAB proteins in chemical synaptic transmission. This mutant exhibits impaired synaptic function, including a rapid activity-dependent reduction in neurotransmitter release and disruption of synaptic vesicle endocytosis. In presynaptic boutons,
Drosophila
DAB and CLATHRIN were highly colocalized within two distinct classes of puncta, including relatively dim puncta that were located at active zones and may reflect endocytic mechanisms operating at neurotransmitter release sites. Finally, broader analysis of endocytic proteins, including DYNAMIN, supported a general role for CLATHRIN-mediated endocytic mechanisms in rapid clearance of neurotransmitter release sites for subsequent vesicle priming and refilling of the release-ready vesicle pool.
Islet amyloid polypeptide demonstrates a persistent capacity to disrupt membrane integrity
Authors: Last Nicholas B. , Rhoades Elizabeth , Miranker Andrew D.
Published: May 2011

Amyloid fiber formation is correlated with pathology in many diseases, including Alzheimer’s, Parkinson’s, and type II diabetes. Although β-sheet–rich fibrillar protein deposits define this class of disorder, increasing evidence points toward small oligomeric species as being responsible for cell dysfunction and death. The molecular mechanism by which this occurs is unknown, but likely involves the interaction of these species with biological membranes, with a subsequent loss of integrity. Here, we investigate islet amyloid polypeptide, which is implicated in the loss of insulin-secreting cells in type II diabetics. We report the discovery of oligomeric species that arise through stochastic nucleation on membranes and result in disruption of the lipid bilayer. These species are stable, result in all-or-none leakage, and represent a definable protein/lipid phase that equilibrates over time. We characterize the reaction pathway of assembly through the use of an experimental design that includes both ensemble and single-particle evaluations. Complexity in the reaction pathway could not be satisfied using a two-state description of membrane-bound monomer and oligomeric species. We therefore put forward a three-state kinetic framework, one of which we conjecture represents a non-amyloid, non-β-sheet intermediate previously shown to be a candidate therapeutic target.
Behavioral thermoregulation by turtle embryos
Authors: Du Wei-Guo , Zhao Bo , Chen Ye , Shine Richard
Published: May 2011

Mobile ectothermic animals can control their body temperatures by selecting specific thermal conditions in the environment, but embryos—trapped within an immobile egg and lacking locomotor structures—have been assumed to lack that ability. Falsifying that assumption, our experimental studies show that even early stage turtle embryos move within the egg to exploit small-scale spatial thermal heterogeneity. Behavioral thermoregulation is not restricted to posthatching life and instead may be an important tactic in every life-history stage.
Photosynthetic electron partitioning between [FeFe]-hydrogenase and ferredoxin:NADP
+
-oxidoreductase (FNR) enzymes in vitro
Authors: Yacoby Iftach , Pochekailov Sergii , Toporik Hila , Ghirardi Maria L. , King Paul W. , Zhang Shuguang
Published: May 2011

Photosynthetic water splitting, coupled to hydrogenase-catalyzed hydrogen production, is considered a promising clean, renewable source of energy. It is widely accepted that the oxygen sensitivity of hydrogen production, combined with competition between hydrogenases and NADPH-dependent carbon dioxide fixation are the main limitations for its commercialization. Here we provide evidence that, under the anaerobic conditions that support hydrogen production, there is a significant loss of photosynthetic electrons toward NADPH production in vitro. To elucidate the basis for competition, we bioengineered a ferredoxin-hydrogenase fusion and characterized hydrogen production kinetics in the presence of Fd, ferredoxin:NADP
+
-oxidoreductase (FNR), and NADP
+
. Replacing the hydrogenase with a ferredoxin-hydrogenase fusion switched the bias of electron transfer from FNR to hydrogenase and resulted in an increased rate of hydrogen photoproduction. These results suggest a new direction for improvement of biohydrogen production and a means to further resolve the mechanisms that control partitioning of photosynthetic electron transport.
Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen
Authors: Evans Michael J. , Smith-Jones Peter M. , Wongvipat John , Navarro Vincent , Kim Sae , Bander Neil H. , Larson Steven M. , Sawyers Charles L.
Published: May 2011

Despite encouraging clinical results with next generation drugs (MDV3100 and abiraterone) that inhibit androgen receptor (AR) signaling in patients with castration-resistant prostate cancer (CRPC), responses are variable and short-lived. There is an urgent need to understand the basis of resistance to optimize their future use. We reasoned that a radiopharmaceutical that measures intratumoral changes in AR signaling could substantially improve our understanding of AR pathway directed therapies. Expanding on previous observations, we first show that prostate-specific membrane antigen (PSMA) is repressed by androgen treatment in multiple models of AR-positive prostate cancer in an AR-dependent manner. Conversely, antiandrogens up-regulate PSMA expression. These expression changes, including increased PSMA expression in response to treatment with the antiandrogen MDV3100, can be quantitatively measured in vivo in human prostate cancer xenograft models through PET imaging with a fully humanized, radiolabeled antibody to PSMA,
64
Cu-J591. Collectively, these results establish that relative changes in PSMA expression levels can be quantitatively measured using a human-ready imaging reagent and could serve as a biomarker of AR signaling to noninvasively evaluate AR activity in patients with CRPC.
Enhancer-driven membrane markers for analysis of nonautonomous mechanisms reveal neuron–glia interactions in
Drosophila
Authors: Han Chun , Jan Lily Yeh , Jan Yuh-Nung
Published: May 2011

Extrinsic factors and the interactions of neurons with surrounding tissues are essential for almost every aspect of neuronal development. Here we describe a strategy of
g
ene
e
xpression with an independent
e
nhancer-driven cellular
m
arker (GEEM) for studying roles of cell–cell interactions and extrinsic factors in the development of the
Drosophila
nervous system. Key to this strategy is robust expression of enhancer-driven transgenic markers in specific neurons. To this end, we have created vectors to achieve bright and even labeling of neuronal processes, easy cloning of enhancer elements, and efficient and flexible generation of transgenic animals. We provide examples of enhancer-driven membrane markers for specific neurons in both the peripheral and central nervous systems and their applications in the study of neuronal projections and connections in the
Drosophila
brain. We further applied GEEM to examine the wrapping of sensory neuron somas by glia during embryonic and larval stages, and neuron–glia interaction during dendrite pruning in live animals, leading to the discovery that glia play critical roles in the severing and degradation of proximal dendrites. The GEEM paradigm should be applicable to the studies of both cell-autonomous and nonautonomous regulations of any cell type.
Rare gene capture in predominantly androgenetic species
Authors: Hedtke Shannon M. , Glaubrecht Matthias , Hillis David M.
Published: May 2011

The long-term persistence of completely asexual species is unexpected. Although asexuality has short-term evolutionary advantages, a lack of genetic recombination leads to the accumulation over time of deleterious mutations. The loss of individual fitness as a result of accumulated deleterious mutations is expected to lead to reduced population fitness and possible lineage extinction. Persistent lineages of asexual, all-female clones (parthenogenetic and gynogenetic species) avoid the negative effects of asexual reproduction through the production of rare males, or otherwise exhibit some degree of genetic recombination. Another form of asexuality, known as androgenesis, results in offspring that are clones of the male parent. Several species of the Asian clam genus
Corbicula
reproduce via androgenesis. We compared gene trees of mitochondrial and nuclear loci from multiple sexual and androgenetic species across the global distribution of
Corbicula
to test the hypothesis of long-term clonality of the androgenetic species. Our results indicate that low levels of genetic capture of maternal nuclear DNA from other species occur within otherwise androgenetic lineages of
Corbicula
. The rare capture of genetic material from other species may allow androgenetic lineages of
Corbicula
to mitigate the effects of deleterious mutation accumulation and increase potentially adaptive variation. Models comparing the relative advantages and disadvantages of sexual and asexual reproduction should consider the possibility of rare genetic recombination, because such events seem to be nearly ubiquitous among otherwise asexual species.
Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8
+
T-cell responses
Authors: Day E. Bridie , Guillonneau Carole , Gras Stephanie , La Gruta Nicole L. , Vignali Dario A. A. , Doherty Peter C. , Purcell Anthony W. , Rossjohn Jamie , Turner Stephen J.
Published: May 2011

Pathogen-specific responses are characterized by preferred profiles of peptide+class I MHC (pMHCI) glycoprotein-specific T-cell receptor (TCR) Variable (V)-region use. How TCRV-region bias impacts TCRαβ heterodimer selection and resultant diversity is unclear. The D
b
PA
224
–specific TCR repertoire in influenza A virus-infected C57BL/6J (B6) mice exhibits a preferred TCRV-region bias toward the TRBV29 gene segment and an optimal complementarity determining region (CDR3) β-length of 6 aa. Despite these restrictions, D
b
PA
224
-specific BV29
+
T cells use a wide array of unique CDR3β sequences. Structural characterization of a single, TRBV29
+
D
b
P
A224
-specific TCRαβ-pMHCI complex demonstrated that CDR3α amino acid side chains made specific peptide interactions, but the CDR3β main chain exclusively contacted peptides. Thus, length but not amino acid sequence was key for recognition and flexibility in Vβ-region use. In support of this hypothesis, retrovirus expression of the D
b
PA
224
-specific TCRVα-chain was used to constrain pairing within a naive/immune epitope-specific repertoire. The retrogenic TCRVα paired with a diversity of CDR3βs in the context of a preferred TCRVβ spectrum. Overall, these data provide an explanation for the combination of TCRV region bias and diversity within selected repertoires, even as they maintain exquisite pMHCI specificity.
Impaired capacity for familiarity after hippocampal damage
Authors: Song Zhuang , Wixted John T. , Hopkins Ramona O. , Squire Larry R.
Published: May 2011

Recognition memory is thought to consist of two components: recollection and familiarity. Whereas it is widely agreed that the hippocampus supports recollection (remembering the episode in which an item was learned), there is uncertainty about whether it also supports familiarity (simply knowing that an item was encountered but without remembering the learning episode). We tested a counterintuitive prediction that follows from the idea that the hippocampus selectively supports recollection. Patients with hippocampal lesions should have strong experiences of familiarity as often as controls do; however, unlike controls, these experiences should not be accompanied by recollection. Accordingly, with methods that allow participants to report whether they remember an item as encountered previously or whether they simply know it is familiar, patients should express strong familiarity (in the absence of recollection) more often than controls. We indexed strong familiarity and recollection for previously studied words by obtaining confidence ratings together with Remember-Know judgments. The result was that patients provided fewer high-confidence Know responses than controls rather than more. Furthermore, the number of Know responses made by patients was substantially less than was predicted if recollection were impaired. This was true regardless of whether the prediction was based on the assumption that recollection and familiarity are independent or dependent processes. These results suggest that hippocampal lesions impair both recollection and familiarity. Unlike many previous studies of these constructs, the prediction (and the result) is independent of any particular theoretical model, and it holds even if Remember-Know judgments are not process-pure indicators of recollection and familiarity.
Mitochondrial DNA mutations in disease and aging
Authors: Park Chan Bae , Larsson Nils-Göran
Published: May 2011

The small mammalian mitochondrial DNA (mtDNA) is very gene dense and encodes factors critical for oxidative phosphorylation. Mutations of mtDNA cause a variety of human mitochondrial diseases and are also heavily implicated in age-associated disease and aging. There has been considerable progress in our understanding of the role for mtDNA mutations in human pathology during the last two decades, but important mechanisms in mitochondrial genetics remain to be explained at the molecular level. In addition, mounting evidence suggests that most mtDNA mutations may be generated by replication errors and not by accumulated damage.
Disconnecting the Golgi ribbon from the centrosome prevents directional cell migration and ciliogenesis
Authors: Hurtado Lidia , Caballero Cristina , Gavilan Maria P. , Cardenas Jesus , Bornens Michel , Rios Rosa M.
Published: May 2011

Mammalian cells exhibit a frequent pericentrosomal Golgi ribbon organization. In this paper, we show that two AKAP450 N-terminal fragments, both containing the Golgi-binding GM130-interacting domain of AKAP450, dissociated endogenous AKAP450 from the Golgi and inhibited microtubule (MT) nucleation at the Golgi without interfering with centrosomal activity. These two fragments had, however, strikingly different effects on both Golgi apparatus (GA) integrity and positioning, whereas the short fragment induced GA circularization and ribbon fragmentation, the large construct that encompasses an additional p150glued/MT-binding domain induced separation of the Golgi ribbon from the centrosome. These distinct phenotypes arose by specific interference of each fragment with either Golgi-dependent or centrosome-dependent stages of Golgi assembly. We could thus demonstrate that breaking the polarity axis by perturbing GA positioning has a more dramatic effect on directional cell migration than disrupting the Golgi ribbon. Both features, however, were required for ciliogenesis. We thus identified AKAP450 as a key determinant of pericentrosomal Golgi ribbon integrity, positioning, and function in mammalian cells.
Peroxisome reintroduction in Hansenula polymorpha requires Pex25 and Rho1
Authors: Saraya Ruchi , Krikken Arjen M. , Veenhuis Marten , van der Klei Ida J.
Published: May 2011

We identified two proteins, Pex25 and Rho1, which are involved in reintroduction of peroxisomes in peroxisome-deficient yeast cells. These are, together with Pex3, the first proteins identified as essential for this process. Of the three members of the Hansenula polymorpha Pex11 protein family—Pex11, Pex25, and Pex11C—only Pex25 was required for reintroduction of peroxisomes into a peroxisome-deficient mutant strain. In peroxisome-deficient pex3 cells, Pex25 localized to structures adjacent to the ER, whereas in wild-type cells it localized to peroxisomes. Pex25 cells were not themselves peroxisome deficient but instead contained a slightly increased number of peroxisomes. Interestingly, pex11 pex25 double deletion cells, in which both peroxisome fission (due to the deletion of PEX11) and reintroduction (due to deletion of PEX25) was blocked, did display a peroxisome-deficient phenotype. Peroxisomes reappeared in pex11 pex25 cells upon synthesis of Pex25, but not of Pex11. Reintroduction in the presence of Pex25 required the function of the GTPase Rho1. These data therefore provide new and detailed insight into factors important for de novo peroxisome formation in yeast.
Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia
Authors: Heltemes-Harris Lynn M. , Willette Mark J.L. , Ramsey Laura B. , Qiu Yi Hua , Neeley E. Shannon , Zhang Nianxiang , Thomas Deborah A. , Koeuth Thearith , Baechler Emily C. , Kornblau Steven M. , Farrar Michael A.
Published: May 2011

As STAT5 is critical for the differentiation, proliferation, and survival of progenitor B cells, this transcription factor may play a role in acute lymphoblastic leukemia (ALL). Here, we show increased expression of activated signal transducer and activator of transcription 5 (STAT5), which is correlated with poor prognosis, in ALL patient cells. Mutations in EBF1 and PAX5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax5 synergize with STAT5 activation to induce ALL, we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice heterozygous for Ebf1 or Pax5. Haploinsufficiency of either Pax5 or Ebf1 synergized with Stat5b-CA to rapidly induce ALL in 100% of the mice. The leukemic cells displayed reduced expression of both Pax5 and Ebf1, but this had little effect on most EBF1 or PAX5 target genes. Only a subset of target genes was deregulated; this subset included a large percentage of potential tumor suppressor genes and oncogenes. Further, most of these genes appear to be jointly regulated by both EBF1 and PAX5. Our findings suggest a model whereby small perturbations in a self-reinforcing network of transcription factors critical for B cell development, specifically PAX5 and EBF1, cooperate with STAT5 activation to initiate ALL.
Non-pharmacological methods of acute pain management
Authors: Mandeville Anna L.
Published: May 2011

Psychological factors are a key part of pain perception as articulated in the neuromatrix model of pain.

Psychoeducational interventions are of significant value in acute pain management and have reduced pain severity, distress, and length of hospital stay.

Mood, beliefs about pain and illness, previous experience of pain, and the behaviour of health care professionals all influence pain perception and response to pain.

Helping patients reappraise the threat value of pain through tailored information giving and where needed cognitive behavioural interventions are practical strategies.

Attention control methods, including clinical hypnosis, are effective in reducing procedural pain.
Evidence and outcomes in acute pain management
Authors: Walker Suellen M.
Published: May 2011

Inadequate control of post-operative pain can be associated with acute morbidity and have adverse effects on recovery and emotional well-being.

The aims of acute pain medicine are reducing pain intensity, control of side effects, hastening rehabilitation, and improving acute and long-term outcomes.

League tables compare the efficacy of analgesics, based on the number-needed-to-treat (NNT) to achieve 50% pain reduction.

Systematic reviews of different interventions for acute pain are conducted and regularly updated in the Cochrane Library.

The second edition of Acute Pain Management: Scientific Evidence by the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine provides a useful summary of the current evidence.
Trauma pain and procedural pain: prevention of chronic pain following acute trauma
Authors: Emmanuel Johan
Published: May 2011

Opioid analgesics should be used with extreme cautions in the self-ventilating head injured patient.

Gastric emptying ceases after trauma. This will limit the efficacy of oral analgesics.

Epidural analgesia has been shown to be an independent predictor of decreased morbidity and mortality in thoracic trauma.

Femoral nerve block is as effective as intravenous morphine in femoral shaft fractures.

Short-term non-steroidal anti-inflammatory drug use has no proven deleterious effects in humans, and should be part of multimodal management.

Trauma is a risk factor for complex regional pain syndrome. Prevention should be aimed at early graded mobilizations with adequate pain relief.

Post-amputation pain encompasses stump pain (nociceptive and neuropathic), and phantom limb pain.
Acute pain in cancer
Authors: Smart James A.
Published: May 2011

Pain in patients with cancer occurs because of a variety of different causes and has both nociceptive and neuropathic pain components.

It is essential that a thorough assessment of the pain is carried out in order to institute appropriate treatment.

Whilst the WHO Pain Ladder is a good place to start, there are many other treatments available to treat pain in cancer.

Any pharmacological or interventional treatment will be more successful if appropriate psychological support is provided.
Acute pain in patients with renal or hepatic impairment
Authors: Moonesinghe Ramini , Mallett Sue
Published: May 2011

The metabolism and excretion of many analgesic drugs will be altered in the presence of renal or hepatic impairment.

Some analgesic drugs can cause renal or hepatic damage.

Protein binding of drugs may be altered by hepatic reduction in production or uraemic displacement from binding sites.

In renal disease, paracetamol is the simple analgesic of choice.

Morphine can be used with care in mild to moderate renal disease, but fentanyl or oxycodone may be better alternatives.

Non-steroidal anti-inflammatory drugs should be avoided in renal disease.

In hepatic disease with significant impairment, doses of morphine must be reduced and the dosage interval lengthened.

Fentanyl should be avoided in severe hepatic disease.
Theories, history, and current taxonomy
Authors: Bennett Michael I.
Published: May 2011

Pain is a complex experience of somatic mechanisms and psychological influences (affective and cognitive) and, as such, is always subjective in nature

The nervous system is capable of substantial plasticity; it can change structure and function in response to development, injury, or experience

Nociceptive or inflammatory pain arises from normal activation of pain pathways...
Neuropathic back pain
Authors: Freynhagen Rainer
Published: May 2011

Approximately 25–30% of patients with chronic low back pain have a neuropathic component, most usually chronic lumbar radicular pain.

Distinguishing between radicular and pseudoradicular syndromes in low back pain may have some clinical relevance but in practice is difficult to achieve.

A neuropathic component in low back pain can be identified through a combination of verbal descriptors and thorough clinical examination including evoking nerve root tension signs or dural irritation (e.g. straight leg raise). There is poor correlation between radiologic imaging and clinical symptoms....
Antidepressants and antiepileptics for neuropathic pain
Authors: McQuay Henry J. , Wiffen Philip
Published: May 2011

Antidepressants and antiepileptics are well-established treatments for neuropathic pain

Clinical trial evidence can be limited in both scope of neuropathic pain conditions studied and duration of treatment. This leaves prescribers to extrapolate evidence to other conditions, and without information on longer-term effects

Lack of head-to-head comparisons results in the use of indirect evidence such as NNTs, but the sample size used to derive NNT values is equally important...
Asynchronous sampling for ultrafast experiments with low momentum compaction at the ANKA ring
Authors: Ibrahimkutty Shyjumon , Issenmann Daniel , Schleef Stefan , Müller Anke-Susanne , Mathis Yves-Laurent , Gasharova Biliana , Huttel Erhart , Steininger Ralph , Göttlicher Jörg , Baumbach Tilo , Bartels Albrecht , Janke Christof , Plech Anton
Published: May 2011

A high-repetition-rate pump–probe experiment is presented, based on the asynchronous sampling approach. The low-α mode at the synchrotron ANKA can be used for a time resolution down to the picosecond limit for the time-domain sampling of the coherent THz emission as well as for hard X-ray pump–probe experiments, which probe structural dynamics in the condensed phase. It is shown that a synchronization of better than 1 ps is achieved, and examples of phonon dynamics of semiconductors are presented.
Evolution of blindness in scolopendromorph centipedes (Chilopoda: Scolopendromorpha): insight from an expanded sampling of molecular data
Authors: Vahtera Varpu , Edgecombe Gregory D. , Giribet Gonzalo
Published: May 2011

Relative to its diversity (34 genera, 700 species), Scolopendromorpha has been undersampled in molecular phylogenetic analyses compared with the other chilopod orders. Previous analyses based on morphology have not resolved several key controversies in systematics and evolutionary morphology unambiguously. Here we apply new molecular and morphological data to scolopendromorph phylogenetics, with a focus on the evolution of blindness. The taxonomic sample includes 19 genera, many lacking previous molecular data, and diverse, cosmopolitan genera of Scolopendridae are sampled by multiple species. Phylogenetic analysis with Direct Optimization used 94 morphological characters and ca. 4.5 kb of sequence data from two nuclear (18S and 28S rRNA) and two mitochondrial (16S rRNA and COI) loci. A single most‐parsimonious cladogram selected after sensitivity analyses resolves Scolopendromorpha as monophyletic, and divides it into a blind clade of three families (Plutoniumidae, Cryptopidae, Scolopocryptopidae) and its ocellate sister group, Scolopendridae. Some species‐rich, cosmopolitan genera (Cormocephalus, Otostigmus, Scolopendra) in Scolopendridae are non‐monophyletic, and in several instances (e.g. New and Old World Scolopendra) relationships are more congruent with geographical distributions than with traditional classifications. The tribe Asanadini is particularly subject to parameter‐sensitivity, nesting in the combined analysis within Scolopendrini but as sister to all other Scolopendrinae for molecular data alone. The total‐evidence tree unambiguously optimizes trunk segmentation: a 23‐segmented trunk has a single origin in the blind clade.

© The Willi Hennig Society 2011.
Lack of evidence of CD40 ligand involvement in transfusion-related acute lung injury
Authors: Tuinman P R , Gerards M C , Jongsma G , Vlaar A P , Boon L , Juffermans N P
Published: May 2011

Activated platelets have been implicated in playing a major role in transfusion-related acute lung injury (TRALI), as platelets can trigger neutrophils, resulting in vascular damage. We hypothesized that binding of platelet CD40 ligand (CD40L) to endothelial CD40 is essential in the onset of TRALI. Mice were challenged with monoclonal major histocompatibility complex (MHC)-1 antibody which induced TRALI, evidenced by pulmonary oedema, accompanied by significantly elevated bronchoalveolar fluid (BALF) levels of total protein and elevated plasma levels of keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2) compared to infusion of isotype antibody (all Ps < 0·05). Treatment with ciglitazone, which inhibits platelet CD40L expression, had no effect on pulmonary and systemic inflammation compared to controls. In addition, treatment with anti-CD40L antibody, which antagonizes all CD40–CD40L interactions, also did not abrogate the TRALI reaction. Furthermore, levels of soluble CD40L were measured in a cohort of cardiac surgery patients, who were followed prospectively for the onset of TRALI after transfusion. Plasma levels of sCD40L at baseline and at time of developing TRALI did not differ between TRALI patients and controls (transfused cardiac surgery patients not developing acute lung injury) (275 ± 192 versus 258 ± 346 and 93 ± 82 versus 93 ± 123 pg/ml, respectively, not significant). In conclusion, these results do not support the idea that the CD40–CD40L interaction is involved in mediating TRALI.