bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase in tracheal investment with beetle size supports hypothesis of oxygen limitation on insect gigantism
Authors: Kaiser Alexander , Klok C. Jaco , Socha John J. , Lee Wah-Keat , Quinlan Michael C. , Harrison Jon F.
Published: August 2007

Recent studies have suggested that Paleozoic hyperoxia enabled animal gigantism, and the subsequent hypoxia drove a reduction in animal size. This evolutionary hypothesis depends on the argument that gas exchange in many invertebrates and skin-breathing vertebrates becomes compromised at large sizes because of distance effects on diffusion. In contrast to vertebrates, which use respiratory and circulatory systems in series, gas exchange in insects is almost exclusively determined by the tracheal system, providing a particularly suitable model to investigate possible limitations of oxygen delivery on size. In this study, we used synchrotron x-ray phase–contrast imaging to visualize the tracheal system and quantify its dimensions in four species of darkling beetles varying in mass by 3 orders of magnitude. We document that, in striking contrast to the pattern observed in vertebrates, larger insects devote a greater fraction of their body to the respiratory system, as tracheal volume scaled with mass
1.29
. The trend is greatest in the legs; the cross-sectional area of the trachea penetrating the leg orifice scaled with mass
1.02
, whereas the cross-sectional area of the leg orifice scaled with mass
0.77
. These trends suggest the space available for tracheae within the leg may ultimately limit the maximum size of extant beetles. Because the size of the tracheal system can be reduced when oxygen supply is increased, hyperoxia, as occurred during late Carboniferous and early Permian, may have facilitated the evolution of giant insects by allowing limbs to reach larger sizes before the tracheal system became limited by spatial constraints.
HIPK2 represses β-catenin-mediated transcription, epidermal stem cell expansion, and skin tumorigenesis
Authors: Wei Guangwei , Ku Stephen , Ma Gene K. , Saito Shin'ichi , Tang Amy A. , Zhang Jiasheng , Mao Jian-Hua , Appella Ettore , Balmain Allan , Huang Eric J.
Published: August 2007

Transcriptional control by β-catenin and lymphoid enhancer-binding factor 1 (LEF1)/T cell factor regulates proliferation in stem cells and tumorigenesis. Here we provide evidence that transcriptional co repressor homeodomain interacting protein kinase 2 (HIPK2) controls the number of stem and progenitor cells in the skin and the susceptibility to develop squamous cell carcinoma. Loss of HIPK2 leads to increased proliferative potential, more rapid G
1
–S transition in cell cycle, and expansion of the epidermal stem cell compartment. Among the critical regulators of G
1
–S transition in the cell cycle, only cyclin D1 is selectively up-regulated in cells lacking HIPK2. Conversely, overexpression of HIPK2 suppresses LEF1/β-catenin-mediated transcriptional activation of cyclin D1 expression. However, deletion of the C-terminal YH domain of HIPK2 completely abolishes its ability to recruit another transcriptional corepressor CtBP and suppress LEF1/β-catenin-mediated transcription. To determine whether loss of HIPK2 leads to increased susceptibility to tumorigenesis, we treat wild-type,
Hipk2
+/−
, and
Hipk2
−/−
mice with the two-stage carcinogenesis protocol. Our results indicate that more skin tumors are induced in
Hipk2
+/−
and
Hipk2
−/−
mutants, with most of the tumors showing shortened incubation time and malignant progression. Together, our results indicate that HIPK2 is a tumor suppressor that controls proliferation by antagonizing LEF1/β-catenin-mediated transcription. Loss of HIPK2 synergizes with activation of H-ras to induce tumorigenesis.
Intrinsic disorder in the C-terminal domain of the
Shaker
voltage-activated K
+
channel modulates its interaction with scaffold proteins
Authors: Magidovich Elhanan , Orr Irit , Fass Deborah , Abdu Uri , Yifrach Ofer
Published: August 2007

The interaction of membrane-embedded voltage-activated potassium channels (Kv) with intracellular scaffold proteins, such as the postsynaptic density 95 (PSD-95) protein, is mediated by the channel C-terminal segment. This interaction underlies Kv channel clustering at unique membrane sites and is important for the proper assembly and functioning of the synapse. In the current study, we address the molecular mechanism underlying Kv/PSD-95 interaction. We provide experimental evidence, based on hydrodynamic and spectroscopic analyses, indicating that the isolated C-terminal segment of the archetypical
Shaker
Kv channel (ShB-C) is a random coil, suggesting that ShB-C belongs to the recently defined class of intrinsically disordered proteins. We show that isolated ShB-C is still able to bind its scaffold protein partner and support protein clustering
in vivo
, indicating that unfoldedness is compatible with ShB-C activity. Pulldown experiments involving C-terminal chains differing in flexibility or length further demonstrate that intrinsic disorder in the C-terminal segment of the
Shaker
channel modulates its interaction with the PSD-95 protein. Our results thus suggest that the C-terminal domain of the
Shaker
Kv channel behaves as an entropic chain and support a “fishing rod” molecular mechanism for Kv channel binding to scaffold proteins. The importance of intrinsically disordered protein segments to the complex processes of synapse assembly, maintenance, and function is discussed.
Repression of Six3 by a corepressor regulates rhodopsin expression
Authors: Manavathi Bramanandam , Peng Shaohua , Rayala Suresh K. , Talukder Amjad H. , Wang Minhua H. , Wang Rui-An , Balasenthil Seetharaman , Agarwal Neeraj , Frishman Laura J. , Kumar Rakesh
Published: August 2007

Here, we provide gain-of-function, loss-of function, and molecular evidence supporting genetic interactions between metastasis associated protein 1 (MTA1) and Six3 and between Six3 and
rhodopsin
. We discovered that MTA1 physically interacts with the
Six3
chromatin in a histone deacetylase-dependent manner, leading to transcriptional suppression of the
Six3
gene. MTA1 is also a Six3-interacting corepressor that contributes to a self-negative regulation of
Six3
transcription by Six3. In contrast, deletion of the
MTA1
alleles in murine embryonic fibroblasts or its knockdown in rat retinal ganglion cells stimulates Six3 expression. MTA1 inactivation in the
MTA1
-null mice results in an elevated Six3 level and proliferation of the retina cells with no obvious abnormities in eye formation. However, unexpectedly, we discovered an enhanced recruitment of Six3 to the
rhodopsin
chromatin in retina from the
MTA1
-null mice; Six3's homeodomain interacts with specific DNA elements in the
rhodopsin
promoter to stimulate its transcription, resulting in increased rhodopsin expression. Further, in holoprosencephaly patients, Six3 protein with a naturally occurring deletion mutation in the helix 3 of the homeodomain does not bind to
rhodopsin
DNA or stimulate
rhodopsin
transcription, implying a potential defective
rhodopsin
pathway in the affected holoprosencephaly patients. Further Six3 cooperates with Crx or NRL in stimulating transcription from the rhodopsin-luc. These findings reveal a previously unrecognized role for the MTA1 as an upstream modifier of Six3 and indicate that Six3 is a direct stimulator of rhodopsin expression, thus revealing a putative role for the MTA1/Six3/rhodopsin pathway in vertebrate eye.
Prophase Microtubule Arrays Undergo Flux-like Behavior in Mammalian Cells
Authors: Ferenz Nick P. , Wadsworth Patricia
Published: August 2007

In higher eukaryotic cells, microtubules within metaphase and anaphase spindles undergo poleward flux, the slow, poleward movement of tubulin subunits through the spindle microtubule lattice. Although a number of studies have documented this phenomenon across a wide range of model systems, the possibility of poleward flux before nuclear envelope breakdown (NEB) has not been examined. Using a mammalian cell line expressing photoactivatable green fluorescent protein (GFP)-tubulin, we observe microtubule motion, both toward and away from centrosomes, at a wide range of rates (0.5–4.5 μm/min) in prophase cells. Rapid microtubule motion in both directions is dynein dependent. In contrast, slow microtubule motion, which occurs at rates consistent with metaphase flux, is insensitive to inhibition of dynein but sensitive to perturbation of Eg5 and Kif2a, two proteins with previously documented roles in flux. Our results demonstrate that microtubules in prophase cells are unexpectedly dynamic and that a subpopulation of these microtubules shows motion that is consistent with flux. We propose that the marked reduction in rate and directionality of microtubule motion from prophase to metaphase results from changes in microtubule organization during spindle formation.
Fused–Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation
Authors: Liu Yajuan , Cao Xuesong , Jiang Jin , Jia Jianhang
Published: August 2007

The seven-transmembrane protein Smoothened (Smo) acts as a signal transducer in the Hedgehog (Hh) pathway that mediates many key developmental processes. In Drosophila, Hh-induced phosphorylation promotes Smo cell-surface accumulation and signaling activity; however, the mechanisms controlling Smo phosphorylation and cell-surface accumulation are still unknown. The intracellular signaling complex containing Fused (Fu) and Costal2 (Cos2) is thought to transduce the Hh signal downstream from Smo. Here, we identify a novel feedback mechanism that regulates Smo through the Fu–Cos2 complex. We found that Hh-induced Smo accumulation is inhibited in fu mutant clones or by expressing a dominant-negative form of Fu, and such inhibition is alleviated by removal of Cos2. Conversely, overexpressing Cos2 blocks Smo accumulation, which is reversed by coexpressing Fu. Cos2 blocks Smo accumulation through its C-terminal Smo-interacting domain, and Fu antagonizes Cos2 by phosphorylating Cos2 at Ser572. Furthermore, we found that Ser572 phosphorylation attenuates the Cos2–Smo interaction and promotes Cos2 instability. Finally, we provided evidence that Fu and Cos2 control Smo cell-surface accumulation by regulating Smo phosphorylation. Our data suggest that Cos2–Smo interaction blocks Hh-induced Smo phosphorylation, and that Fu promotes Smo phosphorylation by antagonizing Cos2.
Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system
Authors: Wakiyama Motoaki , Takimoto Koji , Ohara Osamu , Yokoyama Shigeyuki
Published: August 2007

MicroRNAs (miRNAs) are incorporated into miRNP complexes and regulate protein expression post-transcriptionally through binding to 3′-untranslated regions of target mRNAs. Here we describe a recapitulation of let-7 miRNA-mediated translational repression in a cell-free system, which was established with extracts prepared from HEK293F cells overexpressing miRNA pathway components. In this system, both the cap and poly(A) tail are required for the translational repression, and let-7 directs the deadenylation of target mRNAs. Our work suggests that let-7 miRNPs containing Argonaute and GW182 impair the synergistic enhancement of translation by the 5′-cap and 3′-poly(A) tail, resulting in translational repression.
The PAS/LOV protein VIVID controls temperature compensation of circadian clock phase and development in Neurospora crassa
Authors: Hunt Suzanne M. , Elvin Mark , Crosthwaite Susan K. , Heintzen Christian
Published: August 2007

Circadian clocks are cellular timekeepers that regulate aspects of temporal organization on daily and seasonal time scales. To allow accurate time measurement, the period lengths of clocks are conserved in a range of temperatures—a phenomenon known as temperature compensation. Temperature compensation of circadian clock period aids in maintaining a stable “target time” or phase of clock-controlled events. Here we show that the Neurospora protein VIVID (VVD) buffers the circadian system against temperature fluctuations. In vvd-null mutants, the circadian period of clock-controlled events such as asexual sporulation (conidiation) is temperature compensated, but the phase of this clock time marker is not. Consistent with delayed conidiation at lower temperatures in vvdKO strains, the levels of vvd gene products in the wild type increase with decreasing temperatures. Moreover, vvdC108A mutants that lack the light function of VVD maintain a dark activity that transiently influences the phase of conidiation, indicating that VVD influences the time of conidiation downstream from the clock. FREQUENCY (FRQ) phosphorylation is altered in a vvdKO strain, suggesting a mechanism by which VVD can influence the timing of clock-controlled processes in the dark. Thus, temperature compensation of clock-controlled output is a key factor in maintaining temperature compensation of the entire circadian system.
Characterization of Phosphopeptides Using a Combination of Immobilized Metal Ion Affinity Media and Direct Analysis by MALDI-TOF-MS: Figure 1.
Authors: Deterding Leesa J. , Cutalo Jenny M. , Tomer Kenneth B.
Published: August 2007

INTRODUCTION

Phosphoproteins and peptides can be bound with high specificity to immobilized metal ions such as Fe3+, Ni2+, and Ga3+. This technique can be used with either on-line or off-line MS analysis. However, elution of the phosphopeptides from the metal ion column prior to MS analysis can result in sample loss. Affinity-bound analytes, including phosphopeptides, can be directly analyzed by MALDI-MS without prior elution from the affinity media. Also, consecutive enzymatic reactions, such as phosphatase or carboxypeptidase Y digestion, can be carried out on affinity-bound peptides. When the affinity-bound phosphopeptides are treated with phosphatase, the number of phosphorylation sites can be determined based on the observation of 80-Da (or multiples of 80 Da) mass shifts in the MALDI-MS of the reaction mixture. Carboxypeptidase Y treatment of the affinity-bound phosphopeptides can also be used to cleave amino acids from the carboxyl terminus, with subsequent direct analysis of the enzymatic products by MALDI-MS to locate the phosphorylation sites on the bound phosphopeptides. This protocol details the preparation and use of Fe3+ or Ga3+ metal IMAC with the on-bead analysis of phosphopeptides by MALDI-MS. Enzymatic digestion of affinity-bound peptides is also described.
Tracking Tagged Molecules in Single Neurons in Intact Zebrafish
Authors: Armisen Ricardo , Gleason Michelle R. , Fetcho Joseph R. , Mandel Gail
Published: August 2007

INTRODUCTION

This protocol describes an approach for monitoring the movement of tagged molecules in single neurons in intact embryonic and larval zebrafish. The intact preparation provides a meaningful context for the physiological event being studied. Other advantages offered by the young zebrafish include direct in vivo imaging, the ability to produce large numbers of labeled embryos easily using microinjection, and the existence of identified sensory circuits that can be exploited to activate a particular cell type. One limitation of this system is the fragility of 2- to 3-d-old embryos, which demands delicate physical manipulation of the fish during all stages preceding and during the experiment. In contrast to brain slices or isolated cells, nearly all original neural connections and sensory components are maintained in the intact preparation, so the occurrence of a downstream event may be precluded (or its manifestation enhanced) by some complex interplay of biological processes that are not fully understood.
Imaging Neuronal Activity with Calcium Indicators in Larval Zebrafish
Authors: Fetcho Joseph R.
Published: August 2007

INTRODUCTION

The ability to image neuronal activity with single-cell resolution in fish is a powerful tool for investigating the neuronal basis of behavior in normal and mutant lines of fish. This protocol describes a method for using calcium indicators to monitor neuronal activity in transparent larval zebrafish. The imaging process involves collecting a confocal time series from the cells of interest. The behavior of interest is elicited during the time series to determine whether the cells increase in intensity in association with the behavior.
Preparing DNA from Saliva for Genotyping
Authors: Sahota Amrik , Brooks Andrew I. , Tischfield Jay A.
Published: August 2007

INTRODUCTION

Saliva may be a viable alternative to blood as a source for DNA, and has the advantage that it is collected noninvasively. This protocol describes the Oragene procedure for DNA extraction from 2-mL saliva samples. It yields high-quality DNA suitable for research and diagnostic applications.
Selective expression of Knot/Collier, a transcriptional regulator of the EBF/Olf‐1 family, endows the Drosophila sensory system with neuronal class‐specific elaborated dendritic patterns
Authors: Hattori Yukako , Sugimura Kaoru , Uemura Tadashi
Published: August 2007

Dendritic tree morphology is a hallmark of cellular diversity in the nervous system, and Drosophila dendritic arborization (da) neurons provide an excellent model system to study its molecular basis. The da neurons are classified into four classes I–IV in the order of increasing branching complexity. A transcriptional regulator of the early B‐cell factor (EBF)/olfactory 1 (Olf‐1) family, Knot (Kn)/Collier (Col) is expressed selectively in class IV neurons, which generate the most expansive and complicated dendritic trees in the four classes. Loss of kn function in class IV neurons greatly reduced the number of their dendritic branches. Conversely mis‐expression of kn in classes I and II produced supernumerary higher‐order branches, whereas class III‐specific short and straight terminal branches was hardly formed by kn mis‐expression. Neither kn loss of function nor mis‐expression were associated with dramatic alterations in the expression patterns of two other transcriptional regulators, Abrupt (Ab) and Cut (Ct), which play important roles in shaping dendritic trees with distinct class specificity from Kn. In contrast, Kn was necessary and sufficient to drive expression of a gene that encodes a class IV‐specific channel protein. Collectively, all of our results suggest that Kn exerts its cell‐autonomous function to control the formation, and possibly the function, of class IV‐like elaborated dendritic arbors.
ER E3 ubiquitin ligase HRD‐1 and its specific partner chaperone BiP play important roles in ERAD and developmental growth in Caenorhabditis elegans
Authors: Sasagawa Yohei , Yamanaka Kunitoshi , Ogura Teru
Published: August 2007

p97 (also called VCP or Cdc48p) and E3 ubiquitin ligases are the key players in retrotranslocation and ubiquitination of substrates in the endoplasmic reticulum‐associated degradation (ERAD) pathways. Although their biochemical properties have been well studied, their cellular functions in development have not been revealed. Here, we investigate cellular functions of p97 and E3 ubiquitin ligases in Caenorhabditis elegans as a model organism. We found that C. elegans possesses three E3 ubiquitin ligases (named as HRD‐1, HRDL‐1 and MARC‐6) like mammals, and that their simultaneous depletion caused extremely delayed growth. By monitoring the expression of an ER chaperone gene, it was revealed that p97 and HRD‐1 play essential roles in unfolded protein response (UPR) and ERAD pathways. We further found that HRD‐1 functions in concert with BiP, and that two BiP paralogues are functionally diversified. HRD‐1 and BiP(HSP‐3) play important roles in the developmental growth and function of intestinal cells, while HRD‐1 and BiP(HSP‐4) in the gonad formation. We propose that E3 ubiquitin ligases function in concert with a specific partner chaperone.
Tasphorura, a new genus of Tullbergiinae (Collembola: Onychiuridae) abundant in Tasmanian Nothofagus forest
Authors: GREENSLADE PENELOPE , RUSEK JOSEF
Published: August 2007

Abstract. Tasphorura, a new genus of onychiurid Collembola, is erected for an unusually coloured species, Tasphorura vesiculata n.sp., found at a single locality in Tasmanian Nothofagus rainforest. Its isolated phyletic position is noted and extremely high densities are recorded. The conservation implications of the restricted distribution shown by this species, which is typical of many rainforest invertebrates, are discussed with reference to increasing utilization and fragmentation of these forests.
A new genus of Eulophidae (Hymenoptera: Chalcidoidea) with remarkable male genitalia
Authors: HANSSON CHRIS TER
Published: August 2007

Abstract. A new genus of the subfamily Entedoninae (Hymenoptera: Chalcidoidea: Eulophidae), Perditomlus, is described. Male genitalia in species of this genus display extraordinary morphological differences to an extent which is unique in the Chalcidoidea, and the utility of this character and of male antenna in species identification is demonstrated. The value of male genitalia in chalcid systematics is discussed, and a possible reason for the exceptional development in Perditomlus is considered. Perditomlus includes thirty‐three species, unless otherwise stated from Mexico: abruptus, angustatus, avirostris, bidenticulatus, bifidus, bilobus, calcaratus, crassiscapus, evanescens, falcispinus, faretus, flexilis, geniculates, grandiculus, hastatus, insternatus, languidiscapus, longiparameratus, magnicaulis, mucronatus, parameratulus, penicillatus (Mexico, U.S.A., Canada), pilosus, pinguiscapus (U.S.A.), planiscapus, porcodon, punctiscapus, sinuiscapus, trispinus. unispinus, verticillatus, woolleyi (Mexico, U.S.A.), and zolnerowichi. Perditomlus is considered most closely related to Omphale Haliday.
First‐instar larvae, courtship and oviposition in Eletica: amending the definition of the Meloidae (Coleoptera: Tenebrionoidea)
Authors: PINTO JOHN D. , BOLOGNA MARCO A. , BOUSEMAN JOHN K.
Published: August 2007

Abstract. The first data are presented on larvae, oviposition, and mating behaviour in the Eleticinae, the most primitive subfamily of Meloidae. Taxa studied include two African species of Electica. Larval descriptions of E.rubripennis and E.wahlbergi are presented, as well as observations of oviposition in E.rubripennis and of courtship leading to copulation in E.wahlbergi. The placement of eggs under bark and the absence of a triungulin larva in both species are unique for the family. They represent plesiotypic traits found in other groups of Tenebrionoidea.
A taxonomic revision of the Hilara maura‐group (Diptera: Empididae) in Europe
Authors: CHVÁLA MILAN
Published: August 2007

Abstract. The European species of the Hilara maura‐group are revised. Three species are described as new to science, namely, H.nitidorella sp.n., H.discalis sp.n. (both temperate Central and Western Europe) and H.mauroides sp.n. (Caucasus, male only). A further five species, H.hybrida Collin, H.femorella Zetterstedt, H.sulcitarsis Strobl, H.tyrolensis Strobl and H.bartaki Straka are redescribed, and H.eumera Loew, 1873 becomes a new synonym of H.nitidula Zetterstedt, 1838. Seven lectotypes are designated. All IS European species are keyed, the main differential characters are illustrated, and additional data on biology and distribution are given. The Hilara maura‐group is recognized as a monophyletic group within the genus, characterized by a set of apomorphous characters, and the hypothetical phylogenetic relationships of the species, classified into four natural complexes, are demonstrated.
A new brachypterous Nusalala species from Costa Rica, with comments on the evolution of flightlessness in brown lacewings (Neuroptera: Hemerobiidae)
Authors: OSWALD JOHN D.
Published: August 2007

Abstract. A new flightless hemerobiid species, Nusalala brachyptera, collected at high elevation in Costa Rica, is described and illustrated, and a variety of data relevant to the evolution of flightlessness in the family Hemerobiidae are reviewed. Flightlessness due to brachyptery has evolved independently in at least five monophyletic [= holophyletic] lineages of the family Hemerobiidae (brown lacewings). Volant hemerobiids are primarily foliage foraging arboreal predators [presumed ancestral condition], while flightless species are predominantly associated with terricolous‐type microhabitats (e.g. ground‐litter, epiphytic mosses) [presumed derived condition]. These differences suggest a significant habitat shift for flightless hemerobiid species, and that the parallel evolution of flightlessness and brachyptery in hemerobiids are shared responses to the conditions of a terricolous existence. The restriction of most flightless hemerobiid species to insular and/or montane/alpine land areas may be related to the typically depauperate nature of the faunas of such areas. This faunal characteristic may facilitate transitions from arboreality to terricolousness by presenting ancestrally arboreal predators such as hemerobiids with novel ecological opportunities in terricolous microhabitats.
Lessons from naked apes and their infections
Authors: Weiss Robin A.
Published: August 2007

Human infections come from two main sources. Our ‘family heirlooms’ have co‐evolved with the host as we diverged from the common ancestor of humans and chimpanzees, and these are often vertically transmitted. Our ‘new acquisitions’ come from cross‐species infections, and these are typically horizontally transmitted. Compared with other apes, naked apes harbor a larger variety of pathogens, acquired from the domesticated and commensal non‐primate species which share our habitat, as well as from exotic species. Thus we are nouveaux riches in our collection of infections or ‘metagenome’ and this is reviewed with particular reference to retroviruses. Nakedness poses a challenge to ectoparasites which is discussed in relation to the origin and evolution of human lice from those of the great apes. As humans have acquired infections horizontally from our closest living relatives, the chimpanzee and the gorilla, might we also have exchanged pathogens with other hominid species?
Rapid modifications of peripheral T‐cell subsets that express CD127 in macaques treated with recombinant IL‐7
Authors: Dereuddre‐Bosquet Nathalie , Vaslin Bruno , Delache Benoit , Brochard Patricia , Clayette Pascal , Aubenque Céline , Morre Michel , Assouline Brigitte , Le Grand Roger
Published: August 2007

Background  Interleukin‐7 (IL‐7) is a key regulator of thymopoiesis and T‐cell homeostasis, which increases blood T‐cell number by enhancing thymic output of naive cells and peripheral proliferation.

Methods  We explored the effects of unglycosylated recombinant simian IL‐7 (rsIL‐7) administration on peripheral T‐cell subpopulations in healthy macaques.

Results  RsIL‐7 was well tolerated. Mean half‐life ranged between 9.3 and 13.9 hours. Blood CD3+CD4+ and CD3+CD8+ lymphocyte counts decreased rapidly after each rsIL‐7 administration, the duration of these effects being dependent on the frequency of administration. At treatment completion, the increased of CD3+ lymphocytes was marked at 100 μg/kg every 2 days. CD3+ lymphocytes that harbour the alpha chain of IL‐7 receptor (CD127) and CD3+CD8+ lymphocytes that expressed the proliferation marker Ki‐67 exhibited a similar initial profile. The expression of the anti‐apoptotic marker Bcl‐2 increased in CD3+ lymphocytes during the treatment and post‐treatment period in a dose/frequency dependent manner.

Conclusion  RsIL‐7 was well tolerated in macaques and induces rapid modifications of T‐cells that express CD127.
Direct stringency comparison of two macaque models (single‐high vs. repeat‐low) for mucosal HIV transmission using an identical anti‐HIV chemoprophylaxis intervention
Authors: Subbarao Shambavi , Ramos Artur , Kim Caryn , Adams Debra , Monsour Michael , Butera Sal , Folks Tom , Otten Ron A.
Published: August 2007

Backgroud  In our previous work, oral chemoprophylaxis with tenofovir disoproxil fumarate (TDF) provided partial protection in rhesus macaques against repeated low‐dose (RL) intrarectal SHIV162p3 exposure.

Methods  Here, we make a direct comparison of these previous findings with data generated using a single high (SH)‐dose challenge strategy.

Results  All 5 (100%) control macaques were infected after a SH challenge and only three of five (60%) TDF‐treated macaques became infected. The remaining two TDF‐treated macaques remained virus‐negative and were susceptible to virus infection upon re‐challenge in the absence of oral TDF. Thus, two of five (40%) TDF‐treated macaques were protected by the pre‐exposure chemoprophylaxis regimen. By comparison with the RL challenge system, only one of four (25%) of TDF‐treated macaques were protected from infection, whereas four of four (100%) control macaques became infected using RL challenges.

Conclusion  Taken together, these findings indicate that the stringency of the RL challenge model for testing antiretroviral interventions is not lower and possibly greater than that of the SH challenge model.
Macaques co‐immunized with SIVgag/pol‐HIVenv and IL‐12 plasmid have increased cellular responses
Authors: Robinson T.M. , Sidhu M.K. , Pavlakis G.N. , Felber B.K. , Silvera P. , Lewis M.G. , Eldridge J. , Weiner D.B. , Boyer J.D.
Published: August 2007

Background  The cell mediated immune profiles following immunization with a recombinant DNA vaccine was assessed in the simian‐human immunodeficiency virus (SHIV) and Macaque model. Earlier work demonstrated increased numbers of antigen specific CD8 and CD4 effector cells able to secrete IFN‐γ.

Method  The vaccine strategy included co‐immunization of a DNA based vaccine alone or in combination with a macaque IL‐12 expressing plasmid (pmacIL12). Antigen activated lymphocytes were studied for activation of a set of immunological molecules.

Results  The current study demonstrates lymphocytes isolated and activated from the group that was immunized with DNA and pmacIL12 had a higher level of IFN‐γ producing cells. We also observed a different immunological profile when comparing the cells isolated from macaques immunized with DNA as compared to those animals that also received pmacIL12.

Conclusion  The observed immune profiles are reflective of the co‐delivery of pmacIL12 and demonstrates that IL‐12 can increase the magnitude and polyfunctionality of the cellular immune response.
Arf GAPs and Their Interacting Proteins
Authors: Inoue Hiroki , Randazzo Paul A.
Published: August 2007

Membrane trafficking and remodeling of the actin cytoskeleton are critical activities contributing to cellular events that include cell growth, migration and tumor invasion. ADP‐ribosylation factor (Arf)‐directed GTPase activating proteins (GAPs) have crucial roles in these processes. The Arf GAPs function in part by regulating hydrolysis of GTP bound to Arf proteins. The Arf GAPs, which have multiple functional domains, also affect the actin cytoskeleton and membranes by specific interactions with lipids and proteins. A description of these interactions provides insights into the molecular mechanisms by which Arf GAPs regulate physiological and pathological cellular events. Here we describe the Arf GAP family and summarize the currently identified protein interactors in the context of known Arf GAP functions.
Dignity and Humour
Authors: Gumbley Walter
Published: August 2007

A well-known humorist, Mr. Stephen Leacock, has decided that Popes and Ecclesiastical dignitaries are as a class deficient in humour, and he extends his condemnation to crowned heads, captains of industry, great writers, thinkers, philanthropists, martyrs, reformers and patriots. Such a sweeping charge it is difficult to challenge, and all we can do is to indicate here and there certain symptoms of a humorous nature latent in the higher clergy and royalty ; we have neither time nor space for the rest of mankind.

Humour, like a verb, is sometimes active and sometimes passive. If active in a subject it either produces wit or appreciates it in another. If passive, it is generally unconscious and consequently the amusement is gathered by others. To be plain, the one so gifted is himself a joke, and his state of mind prevents him from being a humorist of the active or real type. The heavens prevent that we should consider the Popes and “the more dignified clergy” in this category of unconscious humorists. The title of this paper is not Dignity versus Humour, and it is far from being our intention to hold up position and responsibility as objects of merriment, though misplaced dignity is one of the foundation stones of the world’s laughter. Few writers would be bold enough to regard the Popes as fit subjects for a joke, but bishops and abbots, more especially the mediaeval ones, have long been looked upon as legitimate prey by writers of amusing (?) fiction. Emperors and other crowned heads have oftentimes aroused amusement, usually a discreet amusement, amongst their subjects ; but there is little humour, conscious or unconscious, in a Captain of Industry, whatever that pompous and preposterous title means.
The Noble Knight and the Six Old Donkeys
Authors: Eden Helen Parry
Published: August 2007

Once upon a time there was a noble knight who led a very merry and graceless life, but at the same time never missed a sermon if he could help it. Of course people jeered at him and said he had better give up sermons if he could not behave himself more suitably. But the knight answered with becoming seriousness, “I trust in time I shall give up my evil ways ; and now although it is true that I do not do all the good I hear about, I am learning what is right against the time when I turn to honest manners in real earnest.”

Well this was an odd way of going to work, and not one I should recommend to anyone I know. But true it is that Heaven notices the little good we do and makes much of it, even though the greater part of our life is evil. The noble knight did mend his ways in time ; and not only gave up his sins, but left the world and all his possessions (which were very great) and became a monk.

Now it happened that at the monastery where he dwelt, getting holier and holier every day, there were six old donkeys which were really past work and no use to anyone at all. The abbot wanted to get rid of them ; and hearing that the noble knight was very well versed in the affairs of the world, he sent him to the fair, accompanied by a lay-brother, to sell the six old donkeys and bring back young ones. This task was by no means to the taste of the noble knight; however, he was a noble monk now, he remembered, and his nobility consisted in obedience ; so off he went.
Is Incompatibilism Intuitive?
Authors: NAHMIAS Eddy , MORRIS STEPHEN G. , NADELHOFFER Thomas , TURNER Jason
Published: August 2007

Incompatibilists believe free will is impossible if determinism is true, and they often claim that this view is supported by ordinary intuitions. We challenge the claim that incompatibilism is intuitive to most laypersons and discuss the significance of this challenge to the free will debate. After explaining why incompatibilists should want their view to accord with pretheoretical intuitions, we suggest that determining whether incompatibilism is in fact intuitive calls for empirical testing. We then present the results of our studies, which put significant pressure on the claim that incompatibilism is intuitive. Finally, we consider and respond to several potential objections to our approach.
Memory, Expression, and Past‐Tense Self‐Knowledge
Authors: CHILD William
Published: August 2007

How should we understand our capacity to remember our past intentional states? And what can we leam from Wittgenstein's treatment of this topic? Three questions are considered. First, what is the relation between our past attitudes and our present beliefs about them? Realism about past attitudes is defended. Second, how should we understand Wittgenstein's view that self‐ascriptions of past attitudes are a kind of “response” and that the “language‐game” of reporting past attitudes is “the primary thing”? The epistemology and metaphysics of past‐tense self‐ascription are examined in the light of those comments, and our acquisition of the concept of past attitudes is discussed. Third, does Wittgenstein give us reason to think that the identity of a past attitude may be constituted, not by anything that was true of the subject at the time, but by her retrospective tendency to self‐ascribe it? It is argued that, contrary to some interpretations, he does not.
The Potential Information Analysis of Seeing
Authors: CAMPBELL Scott
Published: August 2007

I argue for a version of the causal analysis of seeing which I call the ‘potential information’ analysis. I proceed initially by considering some standard causal analyses, those of Tye and Jackson. 1 show that these analyses are too weak, for they allow cases of hallucination to count as seeing. 1 argue that what is central to seeing is that our visual experiences provide a means of gaining true beliefs about objects. This, however, does not mean that we must actually gain true beliefs about objects in any particular case. Rather, what must be the case is that a perceiver of our sort could gain true beliefs about objects on the basis of experiences like ours. 1 defend this analysis against various objections, making important qualifications to it as 1 do so.
Can There Be Full Excuses for Morally Wrong Actions?*
Authors: RIVERA‐LÓPEZ Eduardo
Published: August 2007

Most people (and philosophers) distinguish between performing a morally wrong action and being blameworthy for having performed that action, and believe that an individual can be fully excused for having performed a wrong action. My purpose is to reject this claim. More precisely, I defend what I call the “Dependence Claim”: A's doing X is wrong only if A is blameworthy for having done X. I consider three cases in which, according to the traditional view, a wrong action could be excused: duress, mental illness, and mistake. I try to show that the reasons for excusing in either case are not relevantly distinguishable from the reasons for claiming that the prima facie wrong action is not wrong all things considered.
The Conception of a Person as a Series of Mental Events
Authors: CAMPBELL Scott
Published: August 2007

It is argued that those who accept the psychological criterion of personal identity, such as Parfit and Shoemaker, should accept what I call the ‘series’ view of a person, according to which a person is a unified aggregate of mental events and states. As well as defending this view against objections, I argue that it allows the psychological theorist to avoid the two lives objection which the ‘animalist’ theorists have raised against it, an objection which causes great difficulties for the conception of a person that most psychological theorists favour, the constitution view. It is also argued that the series view allows that people can body swap and teleport, which the constitution view–which takes a person to be a physical object (but a distinct physical object from the human being)–has great trouble with.
Convenient Preparation of Chiral Dipyrrolylmethanes Containing a Chiral Moiety
Authors: Cozzi Pier Giorgio , Gambarotta Sandro , Monari Magda , Zoli Luca
Published: August 2007

A variety of chiral bis-pyrroles have been made readily accessible via acid-catalyzed condensation of chiral ketones with pyrrole. Three representative chiral ketones 2-4 taken from the chiral pool were transformed into the corresponding bis-pyrrole derivatives in a straightforward acid-catalyzed condensation. Chiral β-hydroxy ketone derivatives, prepared through proline-catalyzed aldol condensation of acetone and an aldehyde, are readily transformed into the corresponding dipyrrolylmethane by the acid-catalyzed condensation carried out in the same conditions. The crystal structure of the chiral dipyrrolylmethane 2 derived from the (-)-menthone was determined.
CALCULATION OF THE TRANSPORT PROPERTIES OF GASEOUS MIXTURES OF CF4 WITH O2, N2, CH4 AND CO2 AT LOW DENSITY USING SEMI-EMPIRICAL INVERSION METHOD
Authors: HAGHIGHI BEHZAD , DJAVANMARDI ALIREZA HASSANI , PAPARI MOHAMMAD MEHDI
Published: August 2007

Viscosity and diffusion coefficients for four equimolar binary gaseous mixtures of CF 4 with O 2, N 2, CH 4 and CO 2 are determined from the extended principle of corresponding states by the inversion technique. The Lennard–Jones 12-6 (LJ 12-6) potential energy function is used as the initial model potential required by the technique. The interaction potential energies from the inversion procedure reproduce viscosity within 1% and diffusion coefficients within 5%.
VALIDATION OF 2D MULTI-BLOCK HIGH-SPEED COMPRESSIBLE TURBULENT FLOW SOLVER
Authors: KHAWAR JAWAD , UL-HAQUE ANWAR , CHAUDHRY SAJID RAZA
Published: August 2007

A 2D multi-block high-speed compressible turbulent flow solver CFD2D based on the Jones and Launders two-equation k –ε turbulence model is developed. Method of solution employed is Finite Volume Method. Its basic algorithm is based on the approximate Riemann solver with the three-step Runge–Kutta time integration. Its additional feature includes Wilcox model for compressibility correction of k–ε turbulence model, Girmaji algebraic Reynolds stress (non-linear stress) model and linear stress model for evaluation of turbulent stresses. For validation purpose, code is applied to a 2D diamond aerofoil and a wedge ramp attached to a flat plate. CFD-predicted results are compared to the experimental results for shock wave and shock wave boundary layer interaction on the trailing edge of the fin. Contour plots are also compared to the Schlieren photographs. Flow simulation shows ability of the code to capture the physics of the flow both qualitatively and quantitatively.
DISCRETE SINGULAR CONVOLUTION (DSC) FOR FREE VIBRATION ANALYSIS OF CONICAL SHELLS WITH VARIOUS BOUNDARY CONDITIONS
Authors: CIVALEK ÖMER
Published: August 2007

This paper gives a relatively novel computational approach, the discrete singular convolution (DSC) algorithm, for the free vibration analysis of isotropic and orthotropic conical shells with different boundary conditions. The governing differential equations of vibration of the shell are formulated using Love's first approximation classical thin shell theory. In the proposed approach, the derivatives in both the governing equations and the boundary conditions are discretized by the method of DSC. Typical numerical results are presented illustrating the effect of various geometric and material parameters. The influence of boundary conditions on the frequency characteristics is also discussed. The obtained results are in excellent agreement with those in the literature.
NUMERICAL SOLUTION OF ISOTHERMAL GAS SPHERE PROBLEM
Authors: GUZEL NURAN , OYLUMLU MESERET TUBA
Published: August 2007

In this paper, we use Padé approximation, to solve a boundary-value problem for an isothermal gas sphere, which is a special form of Lane–Emden equation. However, in general, the solution of Lane–Emden equation cannot be given analytically. This type of non-linear differential equations can be solved only numerically. An example is presented to show the ability of the method for Lane–Emden differential equation. Numerical solutions to the isothermal gas sphere have been discussed. We use MAPLE computer algebra systems for numerical calculations [Frank (1996)].
MODIFIED VIRTUAL CRACK-CLOSURE TECHNIQUE USING SPECTRAL ELEMENT METHOD
Authors: KUMAR A. , GOPALAKRISHNAN S. , CHAKRABORTY A.
Published: August 2007

This paper presents a general Chebyshev Spectral Element Method (CSEM) for obtaining strain-energy release rates for crack growth in two-dimensional isotropic materials. The procedure uses virtual crack-closure method. This method is developed for different orders of CSEM and suitable expressions for energy release rates are obtained. These expressions are evaluated by applying them to two Mode-I and two Mixed-mode problems. Two different classes of spectral elements (SEs) are formulated using Chebyshev interpolating functions, the inconsistent conventional SE formulation and the field consistent SE formulation. The convergence is investigated using both the formulations. A relative study on the efficiency of the CSEM with increasing order of polynomials is clearly brought out. The effect of crack-tip element size is also studied. It is observed that field consistent formulation always gives better results compared to inconsistent formulation. Comparisons with results from the literature for these problems show the efficiency of the CSEM.
DERIVATION OF PARTICULAR SOLUTIONS USING CHEBYSHEV POLYNOMIAL BASED FUNCTIONS
Authors: CHEN C. S. , LEE SUNGWOOK , HUANG C.-S.
Published: August 2007

In this paper, we propose a simple and direct numerical procedure to obtain particular solutions for various types of differential equations. This procedure employs the power series expansion of a differential operator. Chebyshev polynomials are selected as basis functions for the approximation of the inhomogeneous terms of the given partial differential equation. This numerical scheme provides a highly efficient and accurate approximation for the evaluation of a particular solution for a variety of classes of partial differential equations. To demonstrate the effectiveness of the proposed scheme, we couple the method of fundamental solutions to solve a modified Helmholtz equation with irregular boundary configuration. The solutions were observed to have high accuracy.
TWO ALGORITHMS FOR FAST INCREMENTAL TRANSITIVE CLOSURE OF SPARSE FUZZY BINARY RELATIONS
Authors: WALLACE MANOLIS , KOLLIAS STEFANOS
Published: August 2007

Sparse fuzzy ordering and partial ordering relations have recently become of great importance in the field of knowledge systems. As the size of the relations utilized in such a framework is extremely large, efficient algorithms are needed for their handling. More specifically, when a part of such a relation is updated, the property of transitivity needs to be re-established in timely manner, as the knowledge system often becomes unusable until this process is completed. In this paper we propose two algorithms for the incremental update of fuzzy transitive relations. The first one focuses on the incremental update of a part of an already transitive relation, while the other tackles the complete transitive closure of any relation. For the average sparse relation, both of the proposed algorithms have considerably smaller computational complexity than the classical approach, which we also prove experimentally via application to real life relations of this type.
Regional Fat Deposition as a Factor in FFA Metabolism
Authors: Votruba Susanne B. , Jensen Michael D.
Published: August 2007

Humans have a large variability in body fat distribution, which has tremendous implications for metabolic health. Obese individuals with an upper-body-fat distribution have increased health complications such as dyslipidemia, hypertension, insulin resistance, and type 2 diabetes in comparison with lower-body-obese individuals. Additionally, females have more body fat, a greater proportion of fat in their lower body, and much less visceral fat than do lean males at the same body mass index. The reasons for these differences in body fat distribution have not been clearly identified but could be important. Herein we review what has been learned about regional differences in triglyceride storage capacity and lipolysis as they relate to the causes and consequences of regional fat accumulation. Both sex and site differences in regional fat storage have been described. In contrast, with the exception of variations between men and women in the contribution of visceral adipose tissue to hepatic FFA delivery, most studies have failed to show important sex differences in regional lipolysis in vivo.