bluuebunny/crossref_metadata_2025 huggingface dataset:
A case report of hepatocellular carcinoma and focal nodular hyperplasia with a myelolipoma in two chimpanzees and a review of spontaneous hepatobiliary tumors in non‐human primates
Authors: Porter Brian F. , Denise Goens S. , Brasky Kathleen M. , Hubbard Gene B.
Published: February 2007

Abstract:  Spontaneous hepatobiliary tumors in non‐human primates are uncommon. Here we report a case of hepatic carcinoma and a case of hepatic focal nodular hyperplasia (FNH) and myelolipoma in two captive chimpanzees. A 16‐year‐old male chimpanzee (4X0392) died after an 8‐month history of hepatic amyloidosis and low‐grade anemia. Necropsy findings included a hepatic neoplasm with highly pleomorphic hepatocytes arranged into irregular thickened trabeculae. The diagnosis was high‐grade hepatocellular carcinoma. A second male chimpanzee (4X0080), 23 years of age, died suddenly of heart failure secondary to cardiomyopathy. An incidental finding at necropsy was a liver mass characterized by multinodularity, prominent fibrous septa, and biliary hyperplasia. These features were consistent with FNH. While 4X0392 had no history of experimental viral exposure, 4X0080 was vaccinated with inactivated hepatitis B virus, an attenuated hepatitis A virus, and was experimentally infected with hepatitis C virus and human immunodeficiency virus. A survey of the literature revealed 68 reported cases of hepatobiliary tumors in non‐human primates, including 12 hepatocellular adenomas, eight cholangiocellular adenomas/cystadenomas, 22 hepatocellular carcinomas, seven cholangiocarcinomas, and seven gallbladder adenocarcinomas. The majority of reported cases have been in prosimians and Old World monkeys. Hepatic neoplasia is rare in chimpanzees. Only four hepatic neoplasms have been reported in chimpanzees, three of which were associated with viral hepatitis. FNH has not been previously described in any non‐human primate.
Orangutan herpesvirus
Authors: Sakulwira Kamol , Theamboonlers Apiradee , Oraveerakul Kanisak , Chaiyabutr Narongsak , Bhattarakosol Parvapan , Poovorawan Yong
Published: February 2007

Abstract:  A male orangutan suffered from ulcers at the buccal mucosa. We obtained swab fluid from the base of both vesicles and ulcers and collected blood for further separation into serum, plasma and peripheral blood mononuclear cells (PBMC) for detection of antibody to herpesvirus by serology and herpesvirus DNA by polymerase chain reaction (PCR) using consensus degenerate primers. Serology was positive for human EBV IgG but negative for Epstein–Barr virus (EBV) immunoglobulin (IgM), as well as for both human cytomegalovirus and herpes simplex virus IgG and IgM. Upon PCR, we obtained a 232‐bp product of virus DNA from PBMC, but not from lesions, serum or plasma. We confirmed the positive result by direct sequencing and compared the nucleotide sequence with other nucleotide sequences applying the BLAST program from GenBank. The sequence was similar to lymphocryptovirus of macaque (93%), marmoset (93%), gorilla (90%) and human EBV (90%). We aligned this sequence with other sequences in GenBank and performed phylogenetic analysis, showing that it probably belongs to the gammaherpesvirus group.
SHIV transmission and susceptibility to re‐exposure through social contact following vaccination with an HIV synthetic peptide‐cocktail: a case study
Authors: Hill Lori R. , Nehete Pramod N. , Schapiro Steven J. , Nehete Bharti P. , Jagannadha Sastry K.
Published: February 2007

Abstract:  An effective vaccine against human immunodeficiency virus (HIV) should not only protect from infection and development of acquired immunodeficiency syndrome (AIDS), but also prevent potential transmission to naïve partners. We recently reported protection of rhesus macaques from chronic simian‐human immunodeficiency virus (SHIV) infection and AIDS by an HIV envelope peptide‐cocktail vaccine. In the present case study, we observed that one of the vaccinated females, with undetectable circulating virus, when housed in a pair with a naïve male, did not transmit the infection over a 35‐week period of social contact. Subsequent experimental challenge of the male with the same SHIV strain resulted in high‐level infection and transmission to its female cage‐mate. However, the virus was undetectable in the female by 12 weeks without further vaccination, validating the multivalent peptide cocktail vaccine approach in the SHIV‐rhesus model, and suggesting its potential utility as an HIV vaccine strategy for humans.
Changes in blood chemistry and hematology variables during aging in captive rhesus macaques (Macaca mulatta). J Med Primatol 30:161–173, 2001
Authors: Smucny D.A. , Allison D.B. , Ingram D.K. , Roth G.S. , Kemnitz J.W. , Kohama S.G. , Lane M.A. , Black A.
Published: February 2007

Abstract:  The Primate Aging Database (PAD) is being developed to assist research using nonhuman primate models for various gerontological applications. We provide now an update of an earlier report providing data on hematological and blood chemistry values for rhesus monkeys across the adult lifespan. These data were collected from several research colonies and have been submitted to rigorous statistical analyses to identify relationships with chronological age.
Dislocation of an upper third molar into the maxillary sinus after a severe trauma: a case report
Authors: Cai Heng‐Xing , Long Xing , Cheng Yong , Li Xiao‐Dan , Jin Hui‐Xi
Published: February 2007

Abstract – Dental injuries are common following facial trauma. This article presents a rare injury: the dislocation of a third molar into the maxillary sinus after complex mandibular and maxillary tuberosity fractures. The possible mechanism and clinical treatment are discussed.
The propeptide of cruzipain − a potent selective inhibitor of the trypanosomal enzymes cruzipain and brucipain, and of the human enzyme cathepsin F
Authors: Reis Flavia C. G. , Costa Tatiana F. R. , Sulea Traian , Mezzetti Alessandra , Scharfstein Julio , Brömme Dieter , Ménard Robert , Lima Ana Paula C. A.
Published: February 2007

Papain‐like cysteine proteases of pathogenic protozoa play important roles in parasite growth, differentiation and host cell invasion. The main cysteine proteases of Trypanosoma cruzi (cruzipain) and of Trypanosoma brucei (brucipain) are validated targets for the development of new chemotherapies. These proteases are synthesized as precursors and activated upon removal of the N‐terminal prodomain. Here we report potent and selective inhibition of cruzipain and brucipain by the recombinant full‐length prodomain of cruzipain. The propeptide did not inhibit human cathepsins S, K or B or papain at the tested concentrations, and moderately inhibited human cathepsin V. Human cathepsin F was very efficiently inhibited (Ki of 32 pm), an interesting finding indicating that cruzipain propeptide is able to discriminate cathepsin F from other cathepsin L‐like enzymes. Comparative structural modeling and analysis identified the interaction between the β1p–α3p loop of the propeptide and the propeptide‐binding loop of mature enzymes as a plausible cause of the observed inhibitory selectivity.
Recent applications of NMR spectroscopy in plant metabolomics
Authors: Ward Jane L. , Baker John M. , Beale Michael H.
Published: February 2007

Recent research has established NMR as a key method for high‐throughput comparative analysis of plant extracts. We discuss recent examples of the use of NMR to provide metabolomic data for various applications in plant science and look forward to the key role that NMR will play in data provision for plant systems biology.
Cloning, characterization and localization of a novel basic peroxidase gene from Catharanthus roseus
Authors: Kumar Santosh , Dutta Ajaswrata , Sinha Alok K. , Sen Jayanti
Published: February 2007

Catharanthus roseus (L.) G. Don produces a number of biologically active terpenoid indole alkaloids via a complex terpenoid indole alkaloid biosynthetic pathway. The final dimerization step of this pathway, leading to the synthesis of a dimeric alkaloid, vinblastine, was demonstrated to be catalyzed by a basic peroxidase. However, reports of the gene encoding this enzyme are scarce for C. roseus. We report here for the first time the cloning, characterization and localization of a novel basic peroxidase, CrPrx, from C. roseus. A 394 bp partial peroxidase cDNA (CrInt1) was initially amplified from the internodal stem tissue, using degenerate oligonucleotide primers, and cloned. The full‐length coding region of CrPrx cDNA was isolated by screening a leaf‐specific cDNA library with CrInt1 as probe. The CrPrx nucleotide sequence encodes a deduced translation product of 330 amino acids with a 21 amino acid signal peptide, suggesting that CrPrx is secretory in nature. The molecular mass of this unprocessed and unmodified deduced protein is estimated to be 37.43 kDa, and the pI value is 8.68. CrPrx was found to belong to a ‘three intron’ category of gene that encodes a class III basic secretory peroxidase. CrPrx protein and mRNA were found to be present in specific organs and were regulated by different stress treatments. Using a β‐glucuronidase–green fluorescent protein fusion of CrPrx protein, we demonstrated that the fused protein is localized in leaf epidermal and guard cell walls of transiently transformed tobacco. We propose that CrPrx is involved in cell wall synthesis, and also that the gene is induced under methyl jasmonate treatment. Its potential involvement in the terpenoid indole alkaloid biosynthetic pathway is discussed.
Synechocystis DrgA protein functioning as nitroreductase and ferric reductase is capable of catalyzing the Fenton reaction
Authors: Takeda Kouji , Iizuka Mayumi , Watanabe Toshihiro , Nakagawa Junichi , Kawasaki Shinji , Niimura Youichi
Published: February 2007

In order to identify an enzyme capable of Fenton reaction in Synechocystis, we purified an enzyme catalyzing one‐electron reduction of t‐butyl hydroperoxide in the presence of FAD and Fe(III)‐EDTA. The enzyme was a 26 kDa protein, and its N‐terminal amino acid sequencing revealed it to be DrgA protein previously reported as quinone reductase [Matsuo M, Endo T and Asada K (1998) Plant Cell Physiol39, 751–755]. The DrgA protein exhibited potent quinone reductase activity and, furthermore, we newly found that it contained FMN and highly catalyzed nitroreductase, flavin reductase and ferric reductase activities. This is the first demonstration of nitroreductase activity of DrgA protein previously identified by a drgA mutant phenotype. DrgA protein strongly catalyzed the Fenton reaction in the presence of synthetic chelate compounds, but did so poorly in the presence of natural chelate compounds. Its ferric reductase activity was observed with both natural and synthetic chelate compounds with a better efficiency with the latter. In addition to small molecular‐weight chemical chelators, an iron transporter protein, transferrin, and an iron storage protein, ferritin, turned out to be substrates of the DrgA protein, suggesting it might play a role in iron metabolism under physiological conditions and possibly catalyze the Fenton reaction under hyper‐reductive conditions in this microorganism.
Lot6p from Saccharomyces cerevisiae is a FMN‐dependent reductase with a potential role in quinone detoxification
Authors: Sollner Sonja , Nebauer Ruth , Ehammer Heidemarie , Prem Anna , Deller Sigrid , Palfey Bruce A. , Daum Günther , Macheroux Peter
Published: February 2007

NAD(P)H:quinone acceptor oxidoreductases are flavoenzymes expressed in the cytoplasm of many tissues and afford protection against the cytotoxic effects of electrophilic quinones by catalyzing a strict two‐electron reduction. Such enzymes have been reported from several mammalian sources, e.g. human, mouse and rat, and from plant species. Here, we report identification of Lot6p (YLR011wp), the first soluble quinone reductase from the unicellular model organism Saccharomyces cerevisiae. Localization studies using an antibody raised against Lot6p as well as microscopic inspection of Lot6p‐GFP demonstrated accumulation of the enzyme in the cytosol of yeast cells. Despite sharing only 23% similarity to type 1 human quinone reductase, Lot6p possesses biochemical properties that are similar to its human counterpart. The enzyme catalyzes a two‐electron reduction of a series of natural and artificial quinone substrates at the expense of either NADH or NADPH. The kinetic mechanism follows a ping‐pong bi–bi reaction scheme, with KM values of 1.6–11 µm for various quinones. Dicoumarol and Cibacron Marine, two well‐known inhibitors of the quinone reductase family, bind to Lot6p and inhibit its activity. In vivo experiments demonstrate that the enzymatic activity of Lot6p is consistent with the phenotype of both Δlot6 and Lot6p overexpressing strains, suggesting that Lot6p may play a role in managing oxidative stress in yeast.
The C‐terminal region of CHD3/ZFH interacts with the CIDD region of the Ets transcription factor ERM and represses transcription of the human presenilin 1 gene
Authors: Pastorcic Martine , Das Hriday K.
Published: February 2007

Presenilins are required for the function of γ‐secretase: a multiprotein complex implicated in the development of Alzheimer's disease (AD). We analyzed expression of the presenilin 1 (PS1) gene. We show that ERM recognizes avian erythroblastosis virus E26 oncogene homolog (Ets) motifs on the PS1 promoter located at −10, +90, +129 and +165, and activates PS1 transcription with promoter fragments containing or not the −10 Ets site. Using yeast two‐hybrid selection we identified interactions between the chromatin remodeling factor CHD3/ZFH and the C‐terminal 415 amino acids of ERM used as bait. Clones contained the C‐terminal region of CHD3 starting from amino acid 1676. This C‐terminal fragment (amino acids 1676–2000) repressed transcription of the PS1 gene in transfection assays and PS1 protein expression from the endogenous gene in SH‐SY5Y cells. In cells transfected with both CHD3 and ERM, activation of PS1 transcription by ERM was eliminated with increasing levels of CHD3. Progressive N‐terminal deletions of CHD3 fragment (amino acids 1676–2000) indicated that sequences crucial for repression of PS1 and interactions with ERM in yeast two‐hybrid assays are located between amino acids 1862 and 1877. This was correlated by the effect of progressive C‐terminal deletions of CHD3, which indicated that sequences required for repression of PS1 lie between amino acids 1955 and 1877. Similarly, deletion to amino acid 1889 eliminated binding in yeast two‐hybrid assays. Testing various shorter fragments of ERM as bait indicated that the region essential for binding CHD3/ZFH is within the amino acid region 96–349, which contains the central inhibitory DNA‐binding domain (CIDD) of ERM. N‐Terminal deletions of ERM showed that residues between amino acids 200 and 343 are required for binding to CHD3 (1676–2000) and C‐terminal deletions of ERM indicated that amino acids 279–299 are also required. Furthermore, data from chromatin immunoprecipitation (ChIP) indicate that CHD3/ZFH interacts with the PS1 promoter in vivo.
Perturbation of membrane microdomains in GLC4 multidrug‐resistant lung cancer cells − modification of ABCC1 (MRP1) localization and functionality
Authors: Marbeuf‐Gueye Carole , Stierle Vérene , Sudwan Paiwan , Salerno Milena , Garnier‐Suillerot Arlette
Published: February 2007

The multidrug resistance‐associated protein transporter ABCC1 (MRP1) is an integral plasma membrane protein involved in the multidrug resistance phenotype. It actively expels a number of cytotoxic molecules from cells. To gain insight into the modulation of the functional properties of this integral membrane protein by cholesterol, a main component of the lipid bilayer, we used multidrug‐resistant GLC4/ADR cells, which overexpress MRP1. Upon altering the plasma membrane cholesterol content of these cells, membrane localization and the activity of MRP1 were analyzed. A detergent‐free methodology was used to separate ‘light’ and ‘heavy’ plasma membrane fractions. Our data show that MRP1 was exclusively found in ‘light’ fractions known as L0 phase membrane microdomains, together with ∼ 23% of gangliosides GM1 and 40% of caveolin‐1. Depletion of the membrane cholesterol level to 40% by treatment with the cholesterol‐chelating agent methyl‐β‐cyclodextrin did not modify MRP1 activity, as evidenced either by the rate of efflux of pirarubicin or that of glutathione. Further cholesterol depletion below 40% yielded both a partial shift of MRP1 to the high‐density fraction and a decrease of its functionality. Taken together, these data suggest that MRP1 funtionality depends on its localization in cholesterol‐rich membrane microdomains.
Differential expression of duplicated LDH‐A genes during temperature acclimation of weatherfishMisgurnus fossilis
Authors: Zakhartsev Maxim , Lucassen Magnus , Kulishova Liliya , Deigweiher Katrin , Smirnova Yuliya A. , Zinov'eva Rina D. , Mugue Nikolay , Baklushinskaya Irina , Pörtner Hans O. , Ozernyuk Nikolay D.
Published: February 2007

Temperature acclimation in poikilotherms entails metabolic rearrangements provided by variations in enzyme properties. However, in most cases the underlying molecular mechanisms that result in structural changes in the enzymes are obscure. This study reports that acclimation to low (5 °C) and high (18 °C) temperatures leads to differential expression of alternative forms of the LDH‐A gene in white skeletal muscle of weatherfish,Misgurnus fossilis. Two isoforms of LDH‐A mRNA were isolated and characterized: a short isoform (= 1332 bp) and a long isoform (= 1550 bp), which both have 5′‐UTRs and ORFs of the same length (333 amino acid residues), but differ in the length of the 3′‐UTR. In addition, these two mRNAs have 44 nucleotide point mismatches of an irregular pattern along the complete sequence, resulting in three amino acid mismatches (Gly214Val; Val304Ile and Asp312Glu) between protein products from the short and long mRNA forms, correspondingly LDH‐Aαand LDH‐Aβsubunits. It is expected that the β‐subunit is more aliphatic due to the properties of the mismatched amino acids and therefore sterically more restricted. According to molecular modelling ofM. fossilisLDH‐A, the Val304Ile mismatch is located in the subunit contact area of the tetramer, whereas the remaining two mismatches surround the contact area; this is expected to manifest in the kinetic and thermodynamic properties of the assembled tetramer. In warm‐acclimated fish the relative expression between α and β isoforms of the LDH‐A mRNA is around 5 : 1, whereas in cold‐acclimated fish expression ofis reduced almost to zero. This indicates that at low temperature the pool of total tetrameric LDH‐A is more homogeneous in terms of α/β‐subunit composition. The temperature acclimation pattern of proportional pooling of subunits with different kinetic and thermodynamic properties of the tetrameric enzyme may result in fine‐tuning of the properties of skeletal LDH‐A, which is in line with previously observed kinetic and thermodynamic differences between ‘cold’ and ‘warm’ LDH‐A purified from weatherfish. Also, an irregular pattern of nucleotide mismatches indicates that these mRNAs are the products of two independently evolving genes, i.e. paralogues. Karyotype analysis has confirmed that the experimental population ofM. fossilisis tetraploid (2n = 100), therefore gene duplication, possibly through tetraploidy, may contribute to the adaptability towards temperature variation.
Number counts and clustering properties of bright distant red galaxies in the UKIDSS Ultra Deep Survey Early Data Release
Authors: Foucaud S. , Almaini O. , Smail I. , Conselice C. J. , Lane K. P. , Edge A. C. , Simpson C. , Dunlop J. S. , McLure R. J. , Cirasuolo M. , Hirst P. , Watson M. G. , Page M. J.
Published: February 2007

We describe the number counts and spatial distribution of 239 distant red galaxies (DRGs), selected from the Early Data Release of the UKIDSS Ultra Deep Survey. The DRGs are identified by their very red infrared colours with (J−K)AB > 1.3, selected over 0.62 deg2 to a 90 per cent completeness limit of KAB≃ 20.7. This is the first time that a large sample of bright DRGs has been studied within a contiguous area, and we provide the first measurements of their number counts and clustering. The population shows strong angular clustering, intermediate between those of K-selected field galaxies and optical/infrared-selected extremely red galaxies. Adopting the redshift distributions determined from other recent studies, we infer a high correlation length of r0∼11 h−1 Mpc. Such strong clustering could imply that our galaxies are hosted by very massive dark matter haloes, consistent with the progenitors of present-day L≳L* elliptical galaxies.
Anisotropic X-ray emission in active galactic nucleus accretion discs
Authors: Nayakshin Sergei
Published: February 2007

Straightforward models of X-ray reflection in the inner region of accretion discs predict that the primary X-ray flux and the flux reflected off the surface of the disc should vary together, albeit with a short light traveltime delay. Most of the observations, however, show that the X-ray flux can vary while the reflected features remain constant. Here we propose a simple explanation for this. In all likelihood, the emission of a moderately optically thick magnetic flare atop an accretion disc is anisotropic. A constant energy release rate in a flare will appear to produce a variable X-ray flux as the flare rotates with the accretion disc anchoring the magnetic tube. The reflector, on the other hand, receives a constant X-ray flux from the flare. Since the reflected emission is azimuthally symmetric, the observer will see a roughly constant reflected flux (neglecting relativistic effects). The model does not produce quasi-periodic oscillations if magnetic flux tubes are sheared out faster than they complete one orbit.
On long-term solar activity at high latitudes
Authors: Li K. J. , Mu J. , Li Q. X.
Published: February 2007

The interesting characteristics of long-term solar activity at high latitudes are reported as follows. (1) Two cyclic behaviours, but in anti-phase with each other, simultaneously exist at high latitudes: the magnetic fluxes in units of gauss of the line-of-sight magnetic fields at latitudes of 60°–70°, possibly representing the amplitude of solar magnetic activity at high latitudes, are in complete anti-phase with the solar activity at middle and low latitudes, usually represented by sunspot numbers. However, the numbers of filaments at latitudes of 60°–90°, possibly representing the complexity of solar magnetic activity at high latitudes, are strangely in complete anti-phase with the magnetic fluxes. (2) Two latitude migrations, but in opposite drift directions relative to each other, exist in a cycle: a poleward migration drifts from the middle latitudes toward the solar poles in the first half of a normal cycle, following an equatorward migration found from the solar poles towards the middle latitudes in the other half of the normal cycle. (3) It is inferred that polar faculae, a frequently observed phenomenon at high latitudes, are more related to the amplitude than to the complexity of solar magnetic activity at high latitudes, and they are in phase with the magnetic fluxes. (4) High-latitude flares, a violent active phenomenon at high latitudes, keep in step with neither the amplitude nor the complexity of solar magnetic activity at high latitudes; they seemingly occur just around the maximum times of both.
Angular distribution of satellite galaxies from the Sloan Digital Sky Survey Data Release 4
Authors: Azzaro Marco , Patiri Santiago G. , Prada Francisco , Zentner Andrew R.
Published: February 2007

We explore the angular distribution of two samples of satellite galaxies orbiting isolated hosts extracted from the Sloan Digital Sky Survey Data Release 4. We find a clear alignment of the satellites along the major axis of their hosts when restricting the analysis to red-coloured hosts. The anisotropy is most pronounced for red satellites of red hosts. We find that the distribution of the satellites about blue, isolated hosts is consistent with isotropy. We show that under the assumption that the true, underlying distribution of satellites of blue hosts exhibits the same anisotropy as the satellites of red hosts, the sample of blue hosts is too small to measure this anisotropy at a statistically significant level. The anisotropy that we detect for satellites about red hosts is independent of the projected radius. In particular, it is evident at large projected distances from the hosts (300 < rp Ϭ 500 kpc).
Fallback accretion in the aftermath of a compact binary merger
Authors: Rosswog Stephan
Published: February 2007

Recent observations of long and short gamma-ray bursts have revealed a puzzling X-ray activity that in some cases continues for hours after the burst. It is difficult to reconcile such time-scales with the viscous time-scales that an accretion disc can plausibly provide. Here I discuss the accretion activity expected from the material that is launched into eccentric but gravitationally bound orbits during a compact binary merger coalescence. From a simple analytical model the time-scales and accretion luminosities that result from fallback in the aftermath of a compact binary merger are derived. For the considered mass range, double neutron star binaries are relatively homogeneous in their fallback luminosities. Neutron star black hole systems show a larger spread in their fallback behaviour. While the model is too simple to make predictions about the detailed time structure of the fallback, it makes reasonable predictions about the gross properties of the fallback. About one hour after the coalescence the fallback accretion luminosity can still be as large as ∼1045 erg s−1, a fraction of which will be transformed into X-rays. Large-scale amplitude variations in the X-ray luminosities can plausibly be caused by gravitational fragmentation, which for the high-eccentricity fallback should occur more easily than in an accretion disc.
Site‐specific Fluorescent Labeling of Poly‐histidine Sequences Using a Metal‐chelating Cysteine
Authors: Krishnan Beena , Szymanska Aneta , Gierasch Lila M.
Published: February 2007

Coupling genetically encoded target sequences with specific and selective labeling strategies has made it possible to utilize fluorescence spectroscopy in complex mixtures to investigate the structure, function, and dynamics of proteins. Thus, there is a growing need for a repertoire of such labeling approaches to deploy based on a given application and to utilize in combination with one another by orthogonal reactivity. We have developed a simple approach to synthesize a fluorescent probe that binds to a poly‐histidine sequence. The amino group of cysteine was converted into nitrilotriacetate to create a metal‐chelating cysteine molecule, Cys‐nitrilotriacetate. Two Cys‐nitrilotriacetate molecules were then cross‐linked using dibromobimane to generate a fluorophore capable of binding a His‐tag on a protein, NTA2‐BM. NTA2‐BM is a potential fluorophore for selective tagging of proteins in vivo.
Synthesis and Biological Activity of a Focused Library of Mitogen‐activated Protein Kinase Phosphatase Inhibitors
Authors: Arnold David M. , Foster Caleb , Huryn Donna M. , Lazo John S. , Johnston Paul A. , Wipf Peter
Published: February 2007

Mitogen‐activated protein kinase phosphatase 1 is a tyrosine phosphatase superfamily member that dephosphorylates and inactivates mitogen‐activated protein kinase substrates, such as p38, c‐Jun‐N‐terminal kinase, and extracellular signal‐related kinase. These mitogen‐activated protein kinase substrates regulate many cellular processes associated with human diseases. In spite of this potential as a molecular target for chemotherapy, however, pharmacologically tractable inhibitors of mitogen‐activated protein kinase phosphatase‐1 have yet to be developed. Based on the results from a high‐throughput screen for small molecule inhibitors of mitogen‐activated protein kinase phosphatase‐1, we designed, synthesized, and evaluated a focused library in an effort to further understand the structural requirements for mitogen‐activated protein kinase phosphatase‐1 inhibitory activity.
Review of the impact of the 1999 Water Regulation in reducing Cryptosporidium contamination risk in groundwater public supplies
Authors: Morris B. , Whitehead E. J.
Published: February 2007

In 2000, the UK introduced a Cryptosporidium oocyst monitoring programme for groundwater public supplies as a consequence of a 1999 amendment to statutory water quality regulations in England and Wales. The programme, which is ongoing and was estimated to have cost c. £12 million (€17.4 million) by the end of 2005, has accumulated the largest and most comprehensive array of data on the presence of oocysts in raw groundwater in the UK to date, with 90 water treatment works subjected to continuous monitoring at one time or another between 2000 and 2005. The programme was preceded by a scrutiny of the future of over 180 groundwater supplies identified as significantly at risk by the 19 water utilities concerned. The results of this process and of the monitoring programme up to 2005 are examined and critically reviewed.
The Case of the Etymologies in Plato'sCratylus
Authors: Thomas Christine J.
Published: February 2007

TheCratyluscontains Plato's most extensive study of the relation of language to reality and to the pursuit of wisdom. Yet the dialogue has remained relatively neglected in efforts to understand Plato's deepest metaphysical and epistemological commitments. The blame for such neglect lies largely in the dialogue's extensive, difficult, even mysterious etymological section. Recent attempts to make sense of the bulk of theCratylusare shedding much welcome light on the important roles that the etymological analyses play in the dialogue and in Plato's philosophy more generally. The article outlines three strategies of interpretation before concluding with the author's own proposal.
Pattern of Distribution of Calcitonin Gene–Related Peptide in the Dorsal Root Ganglion of Animal Models of Diabetes Mellitus
Authors: ADEGHATE ERNEST , RASHED HAMEED , RAJBANDARI SATYAN , SINGH JAIPAUL
Published: February 2007

Abstract:  This article examined the pattern of distribution of calcitonin gene–related peptide (CGRP) in the dorsal root ganglion (DRG) of normal and diabetic Wistar, Zucker lean, and Goto‐Kakizaki (GK) rats to determine whether there are changes in the number and pattern of distribution of CGRP‐positive neurons after the onset of latent or overt diabetes. Type 1 diabetes mellitus was induced in Wistar rats by a single dose of streptozotocin (STZ) given intraperitoneally (60 mg/kg body weight). Four weeks after the induction of diabetes mellitus, diabetic (n= 6) and normal (n= 6), Zucker lean (n= 6), and GK (n= 6) rats were anesthetized with chloral hydrate and their DRGs were removed and processed for immunohistochemistry. CGRP‐positive neurons were observed in the DRG of normal and diabetic Wistar, Zucker lean (nondiabetic), and GK (animal model of type 2 diabetes) rats. CGRP was present in small‐, medium‐, and large‐sized neurons of the DRG in these three animal models. Only a small percentage of large‐sized neurons contains CGRP. The number of CGRP‐positive neurons was significantly (P < 0.05) reduced in STZ‐induced diabetic Wistar and GK rats compared to normal Wistar and Zucker lean rats. Moreover, the quantity of CGRP‐containing varicose nerves was less in diabetic Wistar and GK rats compared to control Wistar and Zucker lean rats. The reduced number of CGRP‐positive neurons in the DRG of GK rats indicated that subjects with latent diabetes may already have dysfunctional CGRP metabolism and thus diabetic neuropathy.
MICROBIOLOGICAL CONSIDERATIONS IN PEDIATRIC AND ADOLESCENT GYNECOLOGY*
Authors: Kotcher Emil
Published: February 2007

The biota of the female reproductive tract reflects the cytologic and physiologic condition of this organ system. The neonate may acquire some of the vaginal infections of its mother during its passage down the birth canal. Lactobacilli, Trichomonas vaginalis, and Candida albicans may be acquired during this period.

After the first two or three weeks and for next 8–10 years, a variety of organisms may be found in the vagina, depending upon the degree of maternal care, familial infections, intravaginal foreign objects, and various other factors. With the onset of pubescence and later sexual activity, a greater variety of organisms may be recovered from the vagina, including the classical venereal pathogens, e.g., Neisseria gonorrhea and Trichomonas vaginalis, which may occur in greater prevalence. Gonorrhea and syphilis have shown an increasing prevalence in urban teenagers in recent years.
EXAMINATION OF THE NORMAL FEMALE NEWBORN
Authors: Howell Doris A.
Published: February 2007

Only after a most meticulous examination can the parents be assured that the girl child is as normal in gross physical appearance as can be determined. The potential for mental and physical growth remains to be revealed, but the initial starting point must be established accurately at birth.
LABORATORY EXAMINATION OF THE PEDIATRIC GYNECOLOGIC PATIENT
Authors: Carrington Elsie R.
Published: February 2007

A rational approach to the diagnosis and management of gynecologic problems in young females depends heavily upon the results of laboratory examinations. Properly selected tests are indispensable in the investigation of sexual ambiguity, certain types of developmental anomalies, sexual precocity, infections, and neoplasms, Many of these can be carried out on an outpatient basis. The more sophisticated, highly specialized techniques, although less frequently required, are performed in an increasing number of centers and all have been made generally available.
DIAGNOSIS AND MANAGEMENT OF VAGINITIS
Authors: Sweeney W. J.
Published: February 2007

Vulvovaginitis in childhood has been defined and a working classification devised. The diagnosis is made by a thorough history, physical examination, and the use of appropriate laboratory aids. Adequate examination of the vagina and cervix and the taking of cultures are absolutely necessary in all cases. Treatment should be individualized on the basis of the etiologic agent involved. The importance of personal cleanliness cannot be overemphasized, as it is probably the most important factor in the treatment.
RADIATION THERAPY IN THE MANAGEMENT OF CHILDREN WITH GYNECOLOGIC CANCERS*
Authors: D'Angio G. J. , Tefft Melvin
Published: February 2007

Treatment of most gynecologic malignancies in the young is primarily surgical even in the case of radiosensitive tumors, because radiotherapy of the female pelvis in children presents many problems. The younger the child at the time of treatment, the more prominent some of these problems become. Though “prophylactic” postoperative radiation is not advocated, radiotherapy can play an important role in controlling residual, recurrent or metastatic disease, notably in the case of the dysgerminoma and the granulosa‐theca‐cell tumor. The combination of surgery, irradiation, and chemotherapy is not only palliative in patients who have disseminated tumors of other histologic types, but it also may be curative. Meticulous accuracy is essential to minimize the untoward effects of radiotherapy.
INDUCED GENITAL ANOMALIES*
Authors: Goldman Allen S. , Bongiovanni Alfred M.
Published: February 2007

The human female fetus has been reported to have varying degrees of virilization of the lower urogenital tract after maternal treatment with androgenic hormones with certain progestins, and rarely with estrogens. Paradoxically, three cases of feminization of male fetuses with varying degrees of hypospadias have been reported to occur after maternal treatment with large doses of either diethyl‐stilbestrol and progesterone, of progesterone alone, or of acetoxyprogesterone (Prodox). An analysis of the human reports and comparable experimental data suggest that the fetal effects of these agents are not analogous to their effects on the end organs in the postnatal animal. Rather, they appear to have some common dose‐dependent teratogenic action during critical periods of genital development in the two sexes. Genetic male infants born with a severe form of congenital adrenal hyperplasia due to a genetic deficiency in activity of 3β‐ hydroxysteroid dehydrogenase (3β‐enzyme) also have incomplete masculine development and hypospadias. Genetic females with this disease are born with a moderate degree of virilization, clitoral hypertrophy, and labial fusion. The 3β‐enzyme is essential in the early biosynthetic pathway of every biologically active steroid hormone.

We have produced an experimental model of this disease by inhibiting rat fetal 3β‐enzyme with a synthetic derivative of testosterone, which differs from the usual product of the 3β‐enzyme primarily by a C‐2α‐cyano group on the androst‐5‐en nucleus. Unlike most enzyme inhibitors, this steroid is tightly and relatively irreversibly bound to the 3β‐enzyme. Evidence is presented that suggests that progestins or estrogens may affect human fetal genital development by inhibiting the activity of the fetal 3β‐enzyme, thereby mimicking the human genetic form and our experimental model of congenital adrenal hyperplasia.
NORMAL PUBERTY AND ADOLESCENCE
Authors: Israel S. Leon
Published: February 2007

The normal process of puberty and adolescence of girls is characterized by orderly growth. It occurs during a span of years during which, in addition to distinct bodily changes, there are psychological alterations leading to psycho‐sexual maturity. The menarche occurs in a setting arranged by an unfolding series of measurable somatic changes, the time of its appearance being a signpost of inestimable value. It is considered to be normal when it appears between the ages of nine and 16. The irregular character of early menstrual cycles is physiologic.
VARIATIONS IN ISOSEXUAL PSEUDOPRECOCIOUS PUBERTY
Authors: Goldfarb Alvin F.
Published: February 2007

Isosexual pseudoprecocious puberty is an unusual pediatric gynecologic problem. By and far the most common form of sexual precocity in the female is constitutional precocious puberty. A thorough evaluation of the child who presents with signs of sexual precocity prior to age nine is essential. The treatment of the problem of isosexual pseudoprecocious puberty is dependent upon the etiology as defined by adequate study of the patient.
FETOLOGY
Authors: Ayd Frank J. , Stewart William H.
Published: February 2007

“Today we are on the threshold of realizing what no one dared to dream a few short decades ago–effective human intervention to prevent or reverse the tragic results of events occurring before birth. As our knowledge grows, and as we make the practical results of that knowledge available to all who need it, we are building a world in which future generations can face the creation of new life without fear.”
A FLUID LIPID‐GLOBULAR PROTEIN MOSAIC MODEL OF MEMBRANE STRUCTURE*
Authors: Singer S. J.
Published: February 2007

The thermodynamic and experimental bases for the lipid‐globular protein mosaic model for the organization of biological membranes, which was proposed some six years ago16 (Lenard and Singer, 1966) and has since been elaborated 6,26 are described. In this model, the integral proteins of membranes are postulated to have an amphipathic structure in the intact membrane; that is, their ionic and highly polar groups are largely located on the membrane surfaces in contact with the aqueous medium, while their nonpolar residues are sequestered from contact with water in the membrane interior. These proteins are intercalated into a discontinuous lipid bilayer in this model. Recent experimental results are consistent with the suggestion that the lipid forms the matrix of the mosaic, and since the membrane lipid is generally fluid rather than crystalline under physiological conditions, the mosaic is expected to be a dynamic one. That is, the membrane appears to be a two‐dimensional viscous solution, with its components able to undergo translational diffusion in the plane of the membrane. Some of the many important functional and physiological corollaries of this structural hypothesis are discussed.
Geographies of War: Perspectives on ‘Resource Wars’
Authors: Le Billon Philippe
Published: February 2007

Natural resources figure prominently in studies of geographies of wars. This article reviews the three main perspectives on so‐called ‘resource wars’: geopolitical, political economy and political ecology. Classical geopolitical perspectives mostly provide ‘realpolitik’ assessments of international tensions over the supply of ‘strategic’ resources. Such geopolitical constructs of ‘resource wars’ frequently oversimplify power relations and provide a fertile ground for critical enquiries. Refining understandings of resource scarcity and power relations, political economy perspectives point at resource dependence and ‘looting’ opportunities as potential risk factors in the onset and duration of armed conflicts. Finally, through greater contextual sensitivity and multiscalar analysis, political ecology perspectives emphasise the diverse forms of violence at play in ‘resource wars’ and stress the importance of identities and territorialities. Bridging and renewing conceptual and methodological approaches drawn from these three perspective could yield yet further insights on so‐called ‘resource wars’ and serve broad objectives of social and environmental justice.
Effect of Pretreatment of Hydrostatic Pressure on Physicochemical Properties of Tilapia Muscle Protein Gels Induced by Setting
Authors: Hsu K.‐C. , Jao C.‐L.
Published: February 2007

ABSTRACT:  Tilapia meat pastes were subjected to pretreatments of hydrostatic pressure (50 to 300 MPa/4 °C/60 min) followed by setting (50 °C/60 min) with or without subsequent cooking (90 °C/20 min) to investigate the changes of rheological properties, gel‐forming ability, whiteness, and protein solubility of gels. The gel by setting only as the control was elastic, rigid, and mainly constituted by covalent bonds. The gel by pretreatments of 50 MPa was similar to the control. A 100‐MPa pretreatment induced a viscous and soft gel with mainly noncovalent bonds. The 200‐MPa pretreatment produced a gel with strongest breaking force and strain compared with all the treatments in this study; moreover, the gel was mainly constituted by hydrogen bonds. A gel induced by a 300‐MPa pretreatment was the most viscous. Via subsequent cooking (90 °C/20 min), all the gels became more rigid and elastic except that induced by a 100‐MPa pretreatment.
Evaluation of Lipid Oxidation and Oxidative Products as Affected by Pork Meat Cut, Packaging Method, and Storage Time during Frozen Storage (−10 °C)
Authors: Park S.Y. , Yoo S.S. , Uh J.H. , Eun J.B. , Lee H.C. , Kim Y.J. , Chin K.B.
Published: February 2007

ABSTRACT:  Lipid oxidation and oxidative volatiles as affected by pork meat cut and packaging method during frozen storage at –10 °C were evaluated. Pork belly cut had higher thiobarbituric acid reactive substance (TBARS) and pH values than did the loin, whereas the loin had higher free fatty acid (FFA) values than that of the belly cut. Peroxide values increased with increased storage time, but were not affected by pork meat cut and packaging method. Volatiles with carbon numbers less than 10 in the belly cut were higher than those in the loin cut, whereas those with carbon numbers greater than 10 in the loin cut were higher than those in belly cut. Most volatiles were decreased with increased storage time, except for propane. Both 4‐pentenal and 4‐methyl‐2‐hexanone in the belly cut showed a positive correlation with FFA, whereas 2,4‐dimethyl‐1‐heptene and 9‐octadecenal in the loin cut were positively correlated with TBARS and FFA, respectively, even though the values were not high enough to predict the degree of lipid oxidation.
Changes in Apple Liquid Phase Concentration throughout Equilibrium in Osmotic Dehydration
Authors: Barat J.M. , Barrera C. , Frías J.M. , Fito P.
Published: February 2007

ABSTRACT:  Previous results on apple tissue equilibration during osmotic dehydration showed that, at very long processing times, the solute concentrations of the fruit liquid phase and the osmotic solution were the same. In the present study, changes in apple liquid phase composition throughout equilibrium in osmotic dehydration were analyzed and modeled. Results showed that, by the time osmosed samples reached the maximum weight and volume loss, solute concentration of the fruit liquid phase was higher than that of the osmotic solution. The reported overconcentration could be explained in terms of the apple structure shrinkage that occurred during the osmotic dehydration with highly concentrated osmotic solutions due to the elastic response of the food structure to the loss of water and intake of solutes. The fruit liquid phase overconcentration rate was observed to depend on the concentration of the osmotic solution, the processing temperature, the sample size, and shape of the cellular tissue.
Modeling Texture Kinetics during Thermal Processing of Potato Products
Authors: Moyano P.C. , Troncoso E. , Pedreschi F.
Published: February 2007

ABSTRACT:  A kinetic model based on 2 irreversible serial chemical reactions has been proposed to fit experimental data of texture changes during thermal processing of potato products. The model links dimensionless maximum force F*MAX with processing time. Experimental texture changes were obtained during frying of French fries and potato chips at different temperatures, while literature data for blanching/cooking of potato cubes have been considered. A satisfactory agreement between experimental and predicted values was observed, with root mean square values (RMSs) in the range of 4.7% to 16.4% for French fries and 16.7% to 29.3% for potato chips. In the case of blanching/cooking, the proposed model gave RMSs in the range of 1.2% to 17.6%, much better than the 6.2% to 44.0% obtained with the traditional 1st‐order kinetics. The model is able to predict likewise the transition from softening to hardening of the tissue during frying.
Melanin coloration in New World orioles II: ancestral state reconstruction reveals lability in the use of carotenoids and phaeomelanins
Authors: M. Hofmann Christopher , W. Cronin Thomas , E. Omland Kevin
Published: February 2007

Although many animals use carotenoids to produce bright yellow, orange, and red colors, an increasing number of studies have found that other pigments, such as melanins, may also be used to produce bright colors. Yet, almost nothing is known about the evolutionary history of this colorful melanin use. We used reflectance spectrometry to determine whether colors in New World orioles were predominantly due to carotenoids, colorful melanins, or a mixture of both. We then used ancestral state reconstruction to infer the directionality of any pigment changes and to test for phylogenetic signal. We found that three oriole taxa likely switched from carotenoid‐ to melanin‐based colors. Several other oriole taxa apparently gained localized melanin coloration, or had coloration that seemed to be produced by a mixture of carotenoids and melanins. We also found little phylogenetic signal on the use of carotenoids or melanins to produce color. However, all pigment changes occurred within one of three major clades of the oriole genus, suggesting there may be signal at deeper phylogenetic levels. These repeated independent switches between carotenoid and melanin colors are surprising in light of the important signaling role that color pigments (especially carotenoids) are thought to play across a wide range of taxa.