bluuebunny/crossref_metadata_2025 huggingface dataset:
Anatomical Mapping of White Matter Hyperintensities (WMH)
Authors: DeCarli Charles , Fletcher Evan , Ramey Vincent , Harvey Danielle , Jagust William J.
Published: December 2004

Background and Purpose—

MRI segmentation and mapping techniques were used to assess evidence in support of categorical distinctions between periventricular white matter hyperintensities (PVWMH) and deep WMH (DWMH). Qualitative MRI studies generally identify 2 categories of WMH on the basis of anatomical localization. Separate pathophysiologies and behavioral consequences are often attributed to these 2 classes of WMH. However, evidence to support these empirical distinctions has not been rigorously sought.

Methods—

MRI analysis of 55 subjects included quantification of WMH volume, mapping onto a common anatomical image, and spatial localization of each WMH voxel. WMH locations were then divided into PVWMH and DWMH on the basis of distance from the lateral ventricles and correlations, with total WMH volume determined. Periventricular distance histograms of WMH voxels were also calculated.

Results—

PVWMH and DWMH were highly correlated with total WMH (
R
2
>0.95) and with each other (
R
2
>0.87). Mapping of all WMH revealed smooth expansion from around central cerebrospinal fluid spaces into more distal cerebral white matter with increasing WMH volume.

Conclusion—

PVWMH, DWMH, and total WMH are highly correlated with each other. Moreover, spatial analysis failed to identify distinct subpopulations for PVWMH and DWMH. These results suggest that categorical distinctions between PVWMH and DWMH may be arbitrary, and conclusions regarding individual relationships between causal factors or behavior for PVWMH and DWMH may more accurately reflect total WMH volume relationships.
Seasonal and Interannual Variations in the Daily Cycle of Winds over the Galápagos
Authors: Hartten Leslie M. , Datulayta Pauline A.
Published: December 2004

While the daily cycle of near-surface winds over the equatorial east Pacific has been studied in some detail, little is known about the daily cycle above the surface layer. Furthermore, the causes of the observed near-surface daily cycle are not well understood. A better understanding of the structure and forcing mechanisms at work on the lower-tropospheric winds over this region may increase our appreciation for the varying importance of local and remote atmospheric and oceanic processes. This study documents the daily cycle of lower-tropospheric winds over one of the Galápagos Islands during the late 1990s, as well as how it varied seasonally and interannually, using half-hourly profiler winds. The well-known zonal semidiurnal tide is evident in the data, as is a diurnal cycle that is predominantly meridional and may be driven by the results of convection over the Andes. In addition, the high vertical resolution of the wind profiles reveals a decoupling of the daily cycle of winds below ∼500 m from those aloft during periods of cold (<23°C) SSTs. This decoupling, which is not evident in long-term mean profiles that effectively filter the daily cycle, may inhibit the vertical mixing of momentum or vertical propagation of tidal or wave signatures over the region.
Statistics of Extreme Synoptic-Scale Wind Speeds in Ensemble Simulations of Current and Future Climate
Authors: van den Brink H. W. , Können G. P. , Opsteegh J. D.
Published: December 2004

Statistical analysis of the wind speeds, generated by a climate model of intermediate complexity, indicates the existence of areas where the extreme value distribution of extratropical winds is double populated, the second population becoming dominant for return periods of order 103 yr. Meteorological analysis of the second population shows that it is caused when extratropical cyclones merge in an extremely strong westerly jet stream such that conditions are generated that are favorable for occurrence of strong diabatic feedbacks. Doubling of the greenhouse gas concentrations changes the areas of second population and increases its frequency. If these model results apply to the real world, then in the exit areas of the jet stream the extreme wind speed with centennial-to-millennial return periods is considerably larger than extreme value analysis of observational records implies.
Healing Potential of Meniscal Tears without Repair in Knees with Anterior Cruciate Ligament Reconstruction
Authors: Yagishita Kazuyoshi , Muneta Takeshi , Ogiuchi Takashi , Sekiya Ichiro , Shinomiya Kenichi
Published: December 2004

Background

Few previous studies have documented the healing potential of meniscal tears that are left to heal without repair.

Purpose

To determine the healing rates of meniscal tears left without repair in knees with anterior cruciate ligament reconstruction.

Study Design

Prospective cohort study.

Methods

One hundred and ninety-two knees were evaluated at the time of anterior cruciate ligament reconstruction and repeat arthroscopy. The healing rates of 41 medial and 42 lateral torn menisci without repair were evaluated by the same 2 surgeons in an identical fashion.

Results

Of 41 medial torn menisci left without repair, 22 (56%) were considered completely healed, 3 (7%) were incompletely healed, 11 (24%) were unhealed, and 5 (10%) had expanded unhealed lesions. Of 42 lateral torn menisci, 31 (74%) were considered completely healed, 2 (5%) were incompletely healed, 6 (14%) were unhealed, and 3 (7%) had expanded unhealed lesions. The healing rate of a medial meniscal tear was length dependent and not related to reconstructed ligament stability.

Conclusions

Stable meniscal tears at the time of anterior cruciate ligament reconstruction possibly could be left in situ. However, longer medial meniscal tears are thought to require additional stabilizing procedures.
cCXCR1 is a receptor for cIL-8 (9E3/cCAF) and its N- and C-terminal peptides and is also activated by hIL-8 (CXCL8)
Authors: Li Qi-Jing , Yao Min , Dueck Melissa , Feugate Jo Ellen , Parpura Vladimir , Martins-Green Manuela
Published: December 2004

Chemokines are chemotactic cytokines that play important roles in immune responses and wound healing, as well as in pathological conditions such as chronic inflammation and tumorigenesis. The chemokines and their receptors are highly conserved and maintain similar functions in different species. One noteworthy exception is the chemokine interleukin (IL)8/CXC ligand 8 and its specific receptor CXCR1, which are found in humans but are not found in the traditional model organisms, mice and rats. As a consequence, we are using model organisms other than mice to study the functions of IL-8 and CXCR1, as well as the mechanisms involved in receptor activation by IL-8. Toward this goal, we have isolated and characterized a new receptor that is highly homologous to human (h)CXCR1, which we named chicken (c)CXCR1. To determine whether this receptor is activated by cIL-8 and its N- and C-terminal peptides and whether it responds to hIL-8, we expressed cCXCR1 in NIH3T3 cells, which naturally lack this receptor, and used single-cell Ca2+ imaging to detect increases in intracellular Ca2+ and immunoblot analysis to detect extracellular signal-regulated kinase 1/2 phosphorylation. We show that cIL-8, its N and C peptides, and hIL-8 activate cCXCR1. We further show that cIL-8 and hIL-8 stimulate chemotaxis of chicken embryonic fibroblasts, cells that express cCXCR1, and that this effect is specific for each chemokine and this receptor. These results strongly suggest that cCXCR1 is the ortholog for hCXCR1 and that chickens can be used as an effective model system to study the functions of IL-8, its terminal peptides, and its specific receptor CXCR1.
Activation of the Mammalian Target of Rapamycin Pathway Acutely Inhibits Insulin Signaling to Akt and Glucose Transport in 3T3-L1 and Human Adipocytes
Authors: Tremblay Frédéric , Gagnon AnneMarie , Veilleux Alain , Sorisky Alexander , Marette André
Published: December 2004

The mammalian target of rapamycin (mTOR) pathway has recently emerged as a chronic modulator of insulin-mediated glucose metabolism. In this study, we evaluated the involvement of this pathway in the acute regulation of insulin action in both 3T3-L1 and human adipocytes. Insulin rapidly (t1/2 = 5 min) stimulated the mTOR pathway, as reflected by a 10-fold stimulation of 70-kDa ribosomal S6 kinase 1 (S6K1) activity in 3T3-L1 adipocytes. Inhibition of mTOR/S6K1 by rapamycin increased insulin-stimulated glucose transport by as much as 45% in 3T3-L1 adipocytes. Activation of mTOR/S6K1 by insulin was associated with a rapamycin-sensitive increase in Ser636/639 phosphorylation of insulin receptor substrate (IRS)-1 but, surprisingly, did not result in impaired IRS-1-associated phosphatidylinositol (PI) 3-kinase activity. However, insulin-induced activation of Akt was increased by rapamycin. Insulin also activated S6K1 and increased phosphorylation of IRS-1 on Ser636/639 in human adipocytes. As in murine cells, rapamycin treatment of human adipocytes inhibited S6K1, blunted Ser636/639 phosphorylation of IRS-1, leading to increased Akt activation and glucose uptake by insulin. Further studies in 3T3-L1 adipocytes revealed that rapamycin prevented the relocalization of IRS-1 from the low-density membranes to the cytosol in response to insulin. Furthermore, inhibition of mTOR markedly potentiated the ability of insulin to increase PI 3,4,5-triphosphate levels concomitantly with an increased phosphorylation of Akt at the plasma membrane, low-density membranes, and cytosol. However, neither GLUT4 nor GLUT1 translocation induced by insulin were increased by rapamycin treatment. Taken together, these results indicate that the mTOR pathway is an important modulator of the signals involved in the acute regulation of insulin-stimulated glucose transport in 3T3-L1 and human adipocytes.
Early Carotid Artery Stenting and Angioplasty in Patients with Acute Ischemic Stroke
Authors: Zaidat Osama O. , Alexander Michael J. , Suarez Jose I. , Tarr Robert W. , Selman Warren R. , Enterline David S. , Smith Tony P.
Published: December 2004

OBJECTIVE:

To determine the safety of early percutaneous endovascular carotid angioplasty and stenting (CAS) after an ischemic stroke.

METHODS:

The neurointerventional database was reviewed for patients who underwent CAS after an acute ischemic stroke in two university hospitals. Clinical and radiological data were reviewed. Outcomes were worsening stroke, new stroke, or stroke-related death up to 30 days after the procedure. Procedure-related complications were also documented.

RESULTS:

A total of 38 patients with 39 procedures were identified. The mean age was 67 ± 15 years; 31 of 38 patients were Caucasian and 24 were female. Hypertension was found in 21 patients, peripheral vascular disease in 12, diabetes in 13, and coronary artery disease in 18. The median initial National Institutes of Health Stroke Scale score was 8. The carotid artery showed severe to high-grade stenosis in 28 patients, dissection was present in 6, and the rest had an acute occlusion treated with thrombolysis followed by CAS. The mean time from stroke onset to CAS was 55 ± 34 hours. The mean degree of stenosis at baseline was 86 ± 11%. In 37 procedures, complete recanalization was achieved, defined as less than 10% residual narrowing; in 2 procedures, the residual stenosis was mild (10–20%). Neurological deterioration occurred after three procedures (7.7%), with minor nondisabling stroke in two and death from intracranial hemorrhage in one.

CONCLUSION:

If deemed necessary and in certain circumstances, early CAS seems to be safe after acute ischemic stroke if infarction volume is small and neurological deficit is mild.
Xanthogranuloma of the Sciatic Nerve: Case Report
Authors: Patil Parag G. , Cummings Thomas J. , Nunley James A. , Friedman Allan H.
Published: December 2004

OBJECTIVE AND IMPORTANCE:

Xanthogranulomas involving the central or peripheral nervous system are extraordinarily rare. None have been reported in the lower extremity. Here, we report and characterize the first case of xanthogranuloma of the sciatic nerve.

CLINICAL PRESENTATION:

A 58-year-old woman presented with poorly localized right back and groin pain. Magnetic resonance imaging studies revealed an enhancing lesion of the sciatic nerve in the right gluteal region.

INTERVENTION:

The sciatic nerve xanthogranuloma was resected without complication.

CONCLUSION:

Our report indicates that xanthogranuloma, although extremely rare, may occur throughout the nervous system. Our evaluation demonstrates that such lesions involving the peripheral nervous system have similar pathological characteristics to xanthogranulomas that more commonly occur in the skin.
Assessing the role of hematopoietic plasticity for endothelial and hepatocyte development by non-invasive lineage tracing
Authors: Stadtfeld Matthias , Graf Thomas
Published: December 2004

Hematopoietic cells have been reported to convert into a number of non-hematopoietic cells types after transplantation/injury. Here, we have used a lineage tracing approach to determine whether hematopoietic plasticity is relevant for the normal development of hepatocytes and endothelial cells, both of which develop in close association with blood cells. Two mouse models were analyzed: vav ancestry mice, in which essentially all hematopoietic cells,including stem cells, irreversibly express yellow fluorescent protein (YFP);and lysozyme ancestry mice, in which all macrophages, as well as a small subset of all other non-myeloid hematopoietic cells, are labeled. Both lines were found to contain YFP+ hepatocytes at similar frequencies,indicating that macrophage to hepatocyte contributions occur in unperturbed mice. However, the YFP+ hepatocytes never formed clusters larger than three cells, suggesting a postnatal origin. In addition, the frequency of these cells was very low (∼1 in 75,000) and only increased two- to threefold after acute liver injury. Analysis of the two mouse models revealed no evidence for a hematopoietic origin of endothelial cells, showing that definitive HSCs do not function as hemangioblasts during normal development. Using endothelial cells and hepatocytes as paradigms, our study indicates that hematopoietic cells are tightly restricted in their differentiation potential during mouse embryo development and that hematopoietic plasticity plays at best a minor role in adult organ maintenance and regeneration.
Smad1, β-catenin and Tcf4 associate in a molecular complex with the Myc promoter in dysplastic renal tissue and cooperate to control Myc transcription
Authors: Hu Ming Chang , Rosenblum Norman D.
Published: December 2004

Renal dysplasia, the major cause of childhood renal failure in humans,arises from perturbed renal morphogenesis and molecular signaling during embryogenesis. Recently, we discovered induction of molecular crosstalk between Smad1 and β-catenin in the TgAlk3QD mouse model of renal medullary cystic dysplasia. Our finding that Myc, a Smad andβ-catenin transcriptional target and effector of renal epithelial dedifferentiation, is misexpressed in dedifferentiated epithelial tubules provided a basis for investigating coordinate transcriptional control by Smad1 and β-catenin in disease. Here, we report enhanced interactions between a molecular complex consisting of Smad1, β-catenin and Tcf4 and adjacent Tcf- and Smad-binding regions located within the Myc promoter in TgAlk3QD dysplastic renal tissue, and Bmp-dependent cooperative control of Myc transcription by Smad1, β-catenin and Tcf4. Analysis of nuclear extracts derived from TgAlk3QD and wild-type renal tissue revealed increased levels of Smad1/β-catenin molecular complexes, and de novo formation of chromatin-associated Tcf4/Smad1 molecular complexes in TgAlk3QD tissues. Analysis of a 476 nucleotide segment of the 1490 nucleotide Myc genomic region upstream of the transcription start site demonstrated interactions between Tcf4 and the Smad consensus binding region and associations of Smad1, β-catenin and Tcf4 with oligo-duplexes that encode the adjacent Tcf- and Smad-binding elements only in TgAlk3QD tissues. In collecting duct cells that express luciferase under the control of the 1490 nucleotide Myc genomic region, Bmp2-dependent stimulation of Myc transcription was dependent on contributions by each of Tcf4, β-catenin and Smad1. These results provide novel insights into mechanisms by which interacting signaling pathways control transcription during the genesis of renal dysplasia.
Metabolism of normothermic woodchucks during prolonged fasting
Authors: Reidy Shannon P. , Weber Jean-Michel
Published: December 2004

The energy metabolism of hibernators has not been characterized for normothermic fasting, and our goal was to quantify oxidative fuel selection of non-hibernating woodchucks Marmota monax during prolonged food deprivation. Indirect calorimetry and nitrogen excretion measurements were used to assess changes in metabolic rate(V̇O2), fuel selection and composition of nitrogen wastes, as well as seasonal differences. For reference, matching experiments were also performed on rabbits. The results show that woodchucks have a higher metabolic rate in summer (271μmol O2 kg-1 min-1) than in spring (200μmol O2 kg-1 min-1) and that fasting-induced metabolic depression is only possible in summer (-25% in 14 days). The metabolic rate of rabbits is high at all times (383 μmol O2 kg-1 min-1), but they show a more rapid depression in response to fasting (-32% in 7 days). Woodchucks have a naturally low reliance on proteins in the fed state (accounting for 8%V̇O2 in spring;17% V̇O2 in summer; vs 28%V̇O2 in rabbits)and are able to decrease it even further during fasting (spring, 5%V̇O2; summer, 6%V̇O2; vs20% V̇O2 in rabbits). This study shows that, apart from their notorious capacity for hibernation, woodchucks are particularly well adapted for normothermic fasting. Their ability to cope with prolonged food deprivation is based on a series of integrated responses eliciting deep metabolic depression and a rapid change in fuel selection to spare limited protein reserves. Information presently available on prolonged fasting suggests that such an ability for metabolic depression, possibly down to minimal levels still compatible with normothermic life, may be common among mammals. In contrast, the extreme protein sparing demonstrated in woodchucks is a unique metabolic feature of fasting champions.
The tube cement of Phragmatopoma californica: a solid foam
Authors: Stewart Russell J. , Weaver James C. , Morse Daniel E. , Waite J. Herbert
Published: December 2004

Phragmatopoma californica is a marine polychaete that builds protective tubes by joining bits of shell and sand grains with a secreted proteinaceous cement. The cement forms a solid foam (closed cells) via covalent crosslinking, as revealed by electron and laser scanning confocal microscopy. The cement contains extractable calcium and magnesium,and non-extractable phosphorus. Amino acid analysis demonstrated that the phosphorus is in the form of phosphoserine and that >90% of serine in the cement (i.e. 28 mol% of residues) is phosphorylated. In addition to previously identified basic proteins, the cement contains a highly acidic polyphosphoserine protein as a major component. We propose a model for the structure and bonding mechanism of the cement that has the following major features: (1) within the secretory pathway of cement gland cells, the electrostatic association of the oppositely charged proteins and divalent cations (Ca2+ and Mg2+) condense the cement proteins into dehydrated secretory granules; (2) the condensation of the cement leads to the separation of the solution into two aqueous phases (complex coacervation) that creates the closed cell foam structure of the cement; (3)rehydration of the condensed cement granules after deposition onto tube particles contributes to the displacement of water from the mineral substrate to facilitate underwater adhesion; and (4) after secretion, covalent cross-linking through oxidative coupling of DOPA gradually solidifies the continuous phase of the cement to set the porous structure.
Being Arising: Buddhist Psychology Books
Authors: Hunter Jeremy P.
Published: December 2004

Being Arising:. Review of Going on Bdngby Mark Epstein and The Positive Psychology of Buddhism and Yoga by Martin Levine .
Toward an anthropology of culpability
Authors: Sundar Nandini
Published: December 2004

Anthropologists concerned with political violence and justice must engage in a comparative examination of culpability for past and ongoing crimes. When powerful states use reparations, truth commissions, or war crime tribunals to attribute culpability to others, including their past selves, they often, paradoxically, legitimize ongoing injustices. As against culturalist explanations for mass violence, which set up a hierarchy of cultures, we need to look at the institutional sites through which public morality is constructed. This approach is illustrated with reference to the killing of Muslims in Gujarat, India, in 2002 and to the invasion of Iraq by the United States in 2003.
Modernity without romance? Masculinity and desire in courtship stories told by young papua new guinean men
Authors: Lipset David
Published: December 2004

Romance has been theoretically associated with the estrangements created by modern individualism. As demonstrated in courtship stories told by young men from the Murik Lakes in Papua New Guinea, the relationship of Murik culture to modernity has not resulted in narratives that privilege a construction of courtship in which the self merges with the beloved. Desire is not defined in terms of romantic love but is set amid events that are scrupulously fixed in the foregrounds of specific times and exact locations. In these tales, representations of personhood are organized by a Homeric chronotope rather than by a romantic one. Although masculinity in Murik culture has undergone important transformations in the 20th century, its sociology has not given way to the discourse of modern individualism.
Please Play with Your Food: An Incomplete Survey of Culinary Wonders in Italian Renaissance Cookery
Authors: parzen jeremy
Published: December 2004

Wonders in Italian Renaissance Cookery

As early as the 1st century C.E., food writers and cooks were devising illusions and theatrical presentations using food and culinary formulas. Roman gourmet Apicius' famous dish "Anchovies without Anchovies" and his utterance that "no one will know what he is eating" are (literally) classic examples of such "culinary wonders."

In recent memory, illustrious chefs like Escoffier at the Savoy in London (who recreated a naval tragedy using poached chicken escalopes) and Abe Lebewohl of the Second Avenue Deli in New York City (who built a replica of the World Trade Center Twin Towers using chopped chicken livers) have made truly extraordinary--if not tasteful--contributions in this field of culinary arts.

Such artifice and conceits found what was perhaps their greatest expression during the Italian Renaissance when the author of the "first modern cookery book," Maestro Martino of Como, documented a series of mirabilia gulae or "wonders of culinary indulgence," including a roast peacock that appears to be alive and spews fire and fishes that appear to swim in a suspended gelatin aquarium.

A survey of his and his contemporaries' recipes reveals that the wholly new genre of culinary writing emerged together with the many other "secret books" of the Italian Renaissance, including miscellanea by famous Renaissance figures like Luca Pacioli.
Mademoiselle Bonafon and the Private Life of Louis XV: Communication Circuits in Eighteenth-Century France
Authors: DARNTON ROBERT
Published: December 2004

ABSTRACT In 1745 a chambermaid in Versailles was shut up in the Bastille for publishing a roman à clef about the sex life of Louis XV. In attempting to get to the bottom of the case, the police uncovered some remarkable information about how oral media and print culture intersected. Their investigation opens up some broad issues related to the history of women, authorship, reading, and public opinion.
Sperm distribution in the genital tract of the bitch following artificial insemination in relation to the time of ovulation
Authors: Rijsselaere T , Van Soom A , Van Cruchten S , Coryn M , Görtz K , Maes D , de Kruif A
Published: December 2004

In the present study, sperm distribution in the genital tract of the bitch following artificial insemination (AI) in relation to the time of ovulation was investigated by histology, scanning electron microscopy (SEM) and flushing. Ten bitches were inseminated intravaginally with 500 × 106spermatozoa: three dogs before ovulation, four dogs during ovulation and three dogs after ovulation. Ovariohysterectomy was performed 24 h after AI. Half of the genital tract was divided into nine segments (cervix, corpus uteri, caudal, middle and cranial uterine horn (UTH), utero–tubal junction (UTJ), isthmus, ampulla and infundibulum), which were processed for histology and SEM. The contralateral UTH and uterine tube (UT) were flushed, and several sperm characteristics were assessed. Histology revealed that the spermatozoa were mainly located in the uterine glands and at the UTJ, while very few spermatozoa were detected in the UT. Insemination during ovulation resulted in higher percentages of glands with spermatozoa in the different parts of the uterus (P< 0.05). Evaluation by SEM showed higher numbers of spermatozoa in several parts of the uterus for bitches inseminated during ovulation (P< 0.05). The mean number of spermatozoa flushed from the UTH and the UT was low. No significant differences in the evaluated sperm quality parameters were found between the flushings of the UTH and the UT. In conclusion, based on our findings, the uterine glands and the UTJ might act as sperm reservoirs in the bitch and sperm transport in the genital tract is affected by the time of AI in relation to ovulation.
Contraception in mice immunized with recombinant zona pellucida subunit 3 proteins correlates with Th2 responses and the levels of interleukin 4 expressed by CD4+ cells
Authors: Clydesdale Gavin , Pekin Jenny , Beaton Sandra , Jackson Ronald J , Vignarajan Soma , Hardy Christopher M
Published: December 2004

The immune responses and contraceptive effect in mice were tested following immunization with purified recombinant zona pellucida (ZP) proteins produced using a vaccinia (v) virus T7 mammalian expression system. Female BALB/c and CBA mice were immunized with recombinant mouse (m) ZP3 (vmZP3) or pig (p) ZPC (vpZPC) using Freund’s adjuvants and boosted three times. Fertility and mean litter size were significantly reduced in groups of BALB/c mice immunized with recombinant vmZP3 and vpZPC compared with controls treated with Freund’s adjuvants alone. In CBA mice, fertility and mean litter size were significantly reduced in groups of animals immunized with vmZP3 but not with vpZPC compared with the controls. Most infertile animals treated with vmZP3 and a single infertile BALB/c mouse treated with vpZPC lacked mature follicles in the ovaries, whilst no abnormalities were detected in the remaining vpZPC treated, fertile vmZP3 treated and control mice. All mice (both fertile and infertile) immunized with vmZP3 and vpZPC produced IgG antibodies, but the levels of total IgG, IgG1 and IgG2a did not correlate with infertility. All BALB/c and CBA mice immunized with vmZP3 and vpZPC showed greater delayed type hypersensitivity responses in the footpads after challenge with their respective antigens than controls, but these did not differ between the fertile and infertile mice. There was, however, a significant correlation between infertility and the levels of the Type 2 T helper cell (Th2) cytokine interleukin 4 produced by CD4+cells from vmZP3 immunized mice in response to stimulation with vmZP3 and this did not apply to the levels of the Type 1 T helper cell (Th1) cytokine interferon gamma or the general proliferation response. The results support the conclusion that induction of Th2 responses in individual mice determines whether infertility develops in response to immunization with zona pellucida proteins.
Antioxidant enzymatic defence systems in sheep corpus luteum throughout pregnancy
Authors: Al-Gubory Kaïs H , Bolifraud Philippe , Germain Guy , Nicole Annie , Ceballos-Bicot Irène
Published: December 2004

The activities of copper, zinc-superoxide dismutase (SOD1), manganese SOD (SOD2), glutathione peroxidase (GPX), glutathione reductase (GSSG-R) and glutathioneS-transferase (GST) were studied in sheep corpora lutea (CL) obtained on days 15, 40, 60, 80 and 128 of pregnancy. Maintained enzymatic activity of SOD1, SOD2, GPX, GSSG-R and GST were found in the sheep CL throughout pregnancy. Enzymatic activity of SOD1, GPX and GST increased significantly from day 15 to day 40 of pregnancy, and thereafter remained constant until day 128. SOD2 and GSSG-R activities were not different between any days of pregnancy examined. Apoptotic luteal cells identified by the terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labelling were very rarely observed, and their incidence (less than 0.5%) was not different between days of pregnancy. These results showed that the activities of antioxidant enzymes in the sheep CL are subject to major changes during early pregnancy, suggesting that the CL of early pregnancy may be rescued from luteolysis through increasing activities of key antioxidant enzymes and inhibition of apoptosis. Maintained levels of antioxidant enzymes in the CL throughout pregnancy may be linked to reactive oxygen species continuously generated in the steroidogenically active luteal cells, and may be involved in the maintenance of luteal steroidogenic activity and cellular integrity.
Ovarian follicular expression of mRNA encoding the type I IGF receptor and IGF-binding protein-2 in sheep following five days of nutritional supplementation with glucose, glucosamine or lupins
Authors: Muñoz-Gutiérrez M , Blache D , Martin G B , Scaramuzzi R J
Published: December 2004

The IGF system is associated with ovarian folliculogenesis. The effect of the IGFs mediated through the type I receptor (IGF-IR) and IGF-binding protein-2 (IGFBP-2), is to regulate the growth and atresia of follicles. To test if the mRNAs for IGF-IR and IGFBP-2 are differentially regulated in the follicle we used nutritional treatments that stimulate folliculogenesis and measured, byin situhybridisation, their mRNAs expression. Groups of five anoestrous Merino ewes were fed wheat straw (control) or the control diet supplemented with lupins (500 g/day). Other ewes were fed the control diet and infused with glucose (50 mmol/h) or with glucosamine (3.5 mmol/h). Intravaginal progestagen sponges were inserted for 12 days, and nutritional treatments were started 5 days before progestagen removal. Follicular development was studied after an artificial follicular phase, simulated by progestagen for 12 days and a regime of GnRH pulses given for 36 h following progestagen withdrawal, when the animals were killed. The ovaries were collected and stored at −80 °C until sectioning at 10 μm. Every 25–28th and 29–32nd section was probed for IGF-IR and IGFBP-2 using35S-labelled oligonucleotide probes. None of the nutritional treatments affected the number or size of follicles positive for IGF-IR, but glucose (P< 0.001) and lupin (P< 0.001) treatments reduced the follicular concentration of mRNA. The nutritional treatments all increased the number of follicles positive for IGFBP-2 (P< 0.05) and reduced their mean diameter (P< 0.05) and with the exception of lupin feeding, the concentration of mRNA (P< 0.05). The results show that all treatments affected the intrafollicular IGF system and suggest that IGF-IR and IGFBP-2 are nutritionally regulated in the follicle. However, the effects of treatments were variable and suggest the existence of multiple regulatory mechanisms that allow for normal variation in composition and balance of the ruminant diet.
Mutations in Su(var)205 and Su(var)3-7 Suppress P-Element-Dependent Silencing in Drosophila melanogaster
Authors: Bushey Daniel , Locke John
Published: December 2004

In Drosophila melanogaster, the w+ transgene in P{lacW}ciDplac is uniformly expressed throughout the adult eye. However, when other P elements are present, this w+ transgene is randomly silenced and this produces a variegated eye phenotype. This P-element-dependent silencing (PDS) is limited to w+ transgenes inserted in a specific region on chromosome 4. In a screen for genetic modifiers of PDS, we isolated mutations in Su(var)205, Su(var)3-7, and two unidentified genes that suppress this variegated phenotype. Therefore, only a few of the genes encoding heterochromatic modifiers act dose dependently in PDS. In addition, we recovered two spontaneous mutations of P{lacW}ciDplac that variegate in the absence of P elements. These P{lacW}ciDplac derivatives have a gypsy element inserted proximally to the P{lacW}ciDplac insert. The same mutations that suppress PDS also suppress w+ silencing from these P{lacW}ciDplac derivative alleles. This indicates that both cis-acting changes in sequence and trans-acting P elements cause a similar change in chromatin structure that silences w+ expression in P{lacW}ciDplac. Together, these results confirm that PDS occurs at P{lacW}ciDplac because of the chromatin structure at this chromosomal position. Studying w+ variegation from P{lacW}ciDplac provides a model for the interactions that can enhance heterochromatic silencing at single P-element inserts.
Haplotype Structure and Phenotypic Associations in the Chromosomal Regions Surrounding Two Arabidopsis thaliana Flowering Time LociSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY781906, AY785055.
Authors: Hagenblad Jenny , Tang Chunlao , Molitor John , Werner Jonathan , Zhao Keyan , Zheng Honggang , Marjoram Paul , Weigel Detlef , Nordborg Magnus
Published: December 2004

The feasibility of using linkage disequilbrium (LD) to fine-map loci underlying natural variation in Arabidopsis thaliana was investigated by looking for associations between flowering time and marker polymorphism in the genomic regions containing two candidate genes, FRI and FLC, both of which are known to contribute to natural variation in flowering. A sample of 196 accessions was used, and polymorphism was assessed by sequencing a total of 17 roughly 500-bp fragments. Using a novel Bayesian algorithm based on haplotype similarity, we demonstrate that LD could have been used to fine-map the FRI gene to a roughly 30-kb region and to identify two common loss-of-function alleles. Interestingly, because of genetic heterogeneity, simple single-marker associations would not have been able to map FRI with nearly the same precision. No clear evidence for previously unknown alleles at either locus was found, but the effect of population structure in causing false positives was evident.
The Enhancer-Blocking Activity of the Fab-7 Boundary From the Drosophila Bithorax Complex Requires GAGA-Factor-Binding Sites
Authors: Schweinsberg Susan , Hagstrom Kirsten , Gohl Daryl , Schedl Paul , Kumar Ram P , Mishra Rakesh , Karch Francois
Published: December 2004

In the work reported here we have analyzed the role of the GAGA factor [encoded by the Trithorax-like (Trl) gene] in the enhancer-blocking activity of Frontabdominal-7 (Fab-7), a domain boundary element from the Drosophila melanogaster bithorax complex (BX-C). One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin. GAGA protein has been shown to localize to the Fab-7 boundary in vivo, and we show that it recognizes sequences from HS1 in vitro. Using two different transgene assays we demonstrate that GAGA-factor-binding sites are necessary but not sufficient for full Fab-7 enhancer-blocking activity. We show that distinct GAGA sites are required for different enhancer-blocking activities at different stages of development. We also show that the enhancer-blocking activity of the endogenous Fab-7 boundary is sensitive to mutations in the gene encoding the GAGA factor Trithorax-like.
The Identities of sym-2, sym-3 and sym-4, Three Genes That Are Synthetically Lethal With mec-8 in Caenorhabditis elegansSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY220985, AY221634, AY223545, and AY372076.
Authors: Yochem John , Bell Leslie R , Herman Robert K
Published: December 2004

On the basis of synthetic lethality, five genes in Caenorhabditis elegans are known to be redundant with the mec-8 gene, which encodes a protein that contains two copies of an RNA recognition motif (RRM) and affects alternative RNA splicing. The molecular identities of two of the redundant genes, sym-1 and sym-5, were previously reported. The remaining three genes have now been cloned, and their synthetically lethal phenotypes with mec-8 are described in more detail. Animals homozygous for mec-8 and sym-2 loss-of-function mutations die during late embryogenesis. The SYM-2 predicted protein contains three RRMs; we propose that SYM-2 and MEC-8 can substitute for each other in promoting the maturation of the transcripts of a vital gene. Animals homozygous for mutations in mec-8 and in either sym-3 or sym-4 have the same striking defect: they arrest development just prior to or just after hatching with a pharynx that appears fully formed but is not properly attached to the body cuticle. sym-3 encodes a protein of unknown function with orthologs in Drosophila and mammals. sym-4 encodes a WD-repeat protein and may also have orthologs in Drosophila and mammals. We propose that SYM-3 and SYM-4 contribute to a common developmental pathway that is redundant with a MEC-8-dependent pathway.
Chromosome-Wide Regulation of Meiotic Crossover Formation in Caenorhabditis elegans Requires Properly Assembled Chromosome Axes
Authors: Nabeshima Kentaro , Villeneuve Anne M , Hillers Kenneth J
Published: December 2004

Most sexually reproducing organisms depend on the regulated formation of crossovers, and the consequent chiasmata, to accomplish successful segregation of homologous chromosomes at the meiosis I division. A robust, chromosome-wide crossover control system limits chromosome pairs to one crossover in most meioses in the nematode Caenorhabditis elegans; this system has been proposed to rely on structural integrity of meiotic chromosome axes. Here, we test this hypothesis using a mutant, him-3(me80), that assembles reduced levels of meiosis-specific axis component HIM-3 along cohesin-containing chromosome axes. Whereas pairing, synapsis, and crossing over are eliminated when HIM-3 is absent, the him-3(me80) mutant supports assembly of synaptonemal complex protein SYP-1 along some paired chromosomes, resulting in partial competence for chiasma formation. We present both genetic and cytological evidence indicating that the him-3(me80) mutation leads to an increased incidence of meiotic products with two crossovers. These results indicate that limiting the amount of a major axis component results in a reduced capacity to communicate the presence of a (nascent) crossover and/or to discourage others in response.
Genomic Deletions of the Drosophila melanogaster Hsp70 Genes
Authors: Gong Wei J , Golic Kent G
Published: December 2004

Homologous recombination can produce directed mutations in the genomes of a number of model organisms, including Drosophila melanogaster. One of the most useful applications has been to delete target genes to generate null alleles. In Drosophila, specific gene deletions have not yet been produced by this method. To test whether such deletions could be produced by homologous recombination in D. melanogaster we set out to delete the Hsp70 genes. Six nearly identical copies of this gene, encoding the major heat-shock protein in Drosophila, are found at two separate but closely linked loci. This arrangement has thwarted standard genetic approaches to generate an Hsp70-null fly, making this an ideal test of gene targeting. In this study, ends-out targeting was used to generate specific deletions of all Hsp70 genes, including one deletion that spanned ∼47 kb. The Hsp70-null flies are viable and fertile. The results show that genomic deletions of varied sizes can be readily generated by homologous recombination in Drosophila.
Maternal isodisomy of the telomeric end of chromosome 2 is responsible for a case of primary hyperoxaluria type 1
Authors: Chevalier‐Porst Françoise , Rolland Marie‐Odile , Cochat Pierre , Bozon Dominique
Published: December 2004

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism, in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of disease, ranging from renal failure in infancy to mere renal stones in late adulthood. This disease is caused by a deficiency of alanine:glyoxylate aminotransferase (AGT), which is encoded by a single copy gene, AGXT, located in 2q37.3. We identified an apparently homozygous, loss‐of‐function, mutation in a patient; the gene defect was present in the heterozygous mother but not in the patient's father. We performed a microsatellite repeat analysis using 13 specific chromosome 2 markers and non‐chromosome 2 minisatellites. Six specific chromosome 2 markers showed an apparently homozygous maternal inheritance while four showed a biparental transmission consistent with paternity (confirmed by minisatellite analysis). Quantitative PCR of AGXT exons 1 and 3 on the patient's and parents genomic DNA revealed the presence of two copies of the gene. This is the first case of PH1 caused by segmental maternal isodisomy of 2q37.3. © 2004 Wiley‐Liss, Inc.
Fryns syndrome with Hirschsprung disease: Support for possible neural crest involvement
Authors: Alkuraya Fowzan S. , Lin Angela E. , Irons Mira B. , Kimonis Virginia E.
Published: December 2004

Fryns syndrome is an autosomal recessive multiple congenital anomaly/mental retardation syndrome characterized by coarse face, distal limb hypoplasia, and diaphragmatic anomalies. We describe a newborn girl with Fryns syndrome and Hirschsprung disease, an association that has been reported in five previous cases. These patients support the hypothesis that the neural crest plays a role in the pathogenesis of Fryns syndrome. Clinically asymptomatic or subtle anomalies that are in the spectrum of neural crest maldevelopment should be sought in all patients with Fryns syndrome including stillbirths, neonatal deaths, as well as long‐term survivors. We suspect that the clinical observation about Hirschsprung disease and Fryns syndrome may provide insight into its molecular mechanisms and candidate genes. © 2004 Wiley‐Liss, Inc.
Characterization of liver involvement in defects of cholesterol biosynthesis: Long‐term follow‐up and review
Authors: Rossi Massimiliano , Vajro Pietro , Iorio Raffaele , Battagliese Antonella , Brunetti‐Pierri Nicola , Corso Gaetano , Di Rocco Maja , Ferrari Paola , Rivasi Francesco , Vecchione Raffaella , Andria Generoso , Parenti Giancarlo
Published: December 2004

Inborn defects of cholesterol biosynthesis are a group of metabolic disorders presenting with mental retardation and multiple congenital anomalies (MCA/MR syndromes). Functional and structural liver involvement has been reported as a rare (2.5–6%) complication of the Smith–Lemli–Opitz syndrome (SLOS) (OMIM: #270400) and it has not been fully characterized. Here, we report on a long‐term follow‐up study of four patients with SLOS, and one case with lathosterolosis (OMIM: #607330) who presented with liver disease and underwent an extensive diagnostic work‐up. Reports of liver involvement in cholesterol biosynthesis defects are reviewed. Two main different patterns of liver involvement emerged: progressive cholestasis, and stable isolated hypertransaminasemia. In our series, the first pattern was found in two patients with SLOS and one with lathosterolosis, and the second in two SLOS cases. Cholestasis was associated with early lethality and normal serum γ‐glutamyl‐transferase (GGT) levels in SLOS, while possible prolonged survival and high GGT levels were seen in lathosterolosis. Hepatic fibrosis was present in both conditions. Liver biopsy performed in one of our SLOS patients with isolated hypertransaminasemia, showed only mild hydropic degeneration of the hepatocytes. The presence of liver involvement in 16% of the SLOS patients diagnosed at our Center suggests that this complication might have been underestimated in previously reported cases, possibly overshadowed by the severity of multiple malformations. Fetal hepatopathy, cholestasis, and isolated hypertransaminasemia can occur also in other disorders of cholesterol biosynthesis, such as mevalonic aciduria (OMIM: +251170), desmosterolosis (OMIM: #602398), Conradi–Hünermann syndrome (OMIM: #302960), Greenberg dysplasia (OMIM: #215140), and Pelger–Huët homozygosity syndrome (#169400). This group of inherited disorders should be considered in the differential diagnosis of patients presenting with liver disease associated with developmental delay and/or multiple malformations. Periodic liver function evaluations are recommended in these patients. © 2004 Wiley‐Liss, Inc.
Velocardiofacial syndrome with single central incisor
Authors: Oberoi Snehlata , Vargervik Karin
Published: December 2004

Three siblings and their mother are reported who all had cytogenetically proven velocardiofacial syndrome (VCFS). One boy had normal dental and craniofacial findings, except for an increased cranial base angle. His sister had only one central incisor in the maxilla. One central incisor had also been missing in the primary dentition. She had no labial frenulum present. Cephalometry showed a small maxillary unit length indicating mild maxillary hypoplasia, an increased anterior face height, steep mandibular plane angle, retruded chin, and a large cranial base angle. Dental measurements showed retroclined lower incisors and increased interincisal angle. A second sister had a cleft of the secondary palate. All permanent teeth were present with the exception of a missing central incisor in the lower jaw: the single lower central incisor was situated in the midline. Her cephalometry showed similar findings as in her sister. All three siblings required palate surgery for speech. Mother was not available for detailed dental and other oral investigations. A single maxillary central incisor has previously been reported in VCFS, but to our knowledge a single central incisor in the mandible has not been reported previously in this entity. © 2004 Wiley‐Liss, Inc.
Down syndrome with pure partial trisomy 21q22 due to a paternal insertion (4;21) uncovered by uncultured amniotic fluid interphase FISH
Authors: Lee J. , Stanley J.R. , Vaz S.A. , Mulvihill J.J. , Wilson P. , Hopcus‐Niccum D. , Li Shibo
Published: December 2004

Objective: To emphasize the usefulness and reliability of fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells in the prenatal diagnosis of common chromosomal aneuploidies. Methods: FISH analyses utilizing centromeric, locus‐specific or whole chromosome paint DNA probes specific for chromosomes X, Y, 13, 18, 21, and 4 were performed on uncultured amniotic fluid cells or the peripheral blood specimen from the father. Routine chromosome analysis was carried out as well. Results: A prenatal case with partial trisomy 21 due to a paternal cryptic insertion (4;21) was ascertained by a rapid overnight FISH on uncultured amniotic fluid cells. The fetus was delivered at term and had classical features of Down syndrome. Conclusion: Our results stress the importance of FISH on uncultured amniotic fluid cells to supplement routine cytogenetics, especially in cases with abnormal ultrasound findings. © 2004 Wiley‐Liss, Inc.