bluuebunny/crossref_metadata_2025 huggingface dataset:
Theorizing modernity conspiratorially: Science, scale, and the political economy of public discourse in explanations of a cholera epidemic
Authors: Briggs Charles L.
Published: December 2004

When some five hundred people in eastern Venezuela died from cholera in 1992–93, officials responded by racializing the dead as “indigenous people” and suggesting that “their culture” was to blame. Stories that circulated in affected communities talked back to official accounts, alleging that the state, global capitalism, and international politics were complicit in a genocidal plot. It is easy to attribute such conspiracy theories to differences of culture and epistemology. I argue, rather, that how political economies position different players in the processes through which public discourses circulate, excluding some communities from access to authoritative sources of information and denying them means of transforming their narratives into public discourse, provides a more fruitful line of analysis. In this article I use—and talk back to—research on science studies, globalization, and public discourse to think about how conspiracy theories can open up new ways for anthropologists to critically engage the contemporary politics of exclusion and help us all find strategies for survival.
Transnational perspectives on sociolinguistic capital among Luso‐Descendants in France and Portugal
Authors: Koven Michèle
Published: December 2004

I argue in this article that language practices and ideologies are central to French–Portuguese transmigrants’ efforts to obtain recognition of legitimate identities in both French and Portuguese national contexts. Drawing on ethnographic work, I describe the encounters of Luso‐Descendants, the adult children of Portuguese migrants, with French and Portuguese monolingual language ideologies. Although these actors’ lives are led transnationally, their life possibilities are structured by sociolinguistic norms centered within two ideologically monolingual nation‐states. This article thus contributes to scholarship about the sociolinguistics of migration by advocating a more transnational approach to the study of migrant populations. Similarly, it contributes to discussions of transnationalism by looking specifically at how language becomes an important site for the enactment of identities within and across multiple national boundaries in the context of the European Union.
Miniaturizing Atatürk Privatization of state imagery and ideology in Turkey
Authors: Özyürek Esra
Published: December 2004

Since the late 1990s Turkish consumers have purchased pictures of Atatürk, the founder of modern Turkey and the most potent symbol of the Turkish state, as popular commodities, displaying them in homes and private businesses. In this article, I argue that these consumer citizens seek to reconcile the memory of Atatürk's state‐led modernity of the 1930s with recent international pressure to achieve a market‐based modernity. As citizens try to mask the authority of secularist state institutions with consumer choice, the market carries state symbolism into new, private spheres, which it previously had not been able to infiltrate.
Real time: Unwinding technocratic and anthropological knowledge
Authors: Riles Annelise
Published: December 2004

“The Bank of Japan is our mother,” bankers in Tokyo sometimes said of Japan's central bank. Drawing on this metaphor as an ethnographic resource, and on the example of central bankers who sought to unwind their own technocratic knowledge by replacing it with a real‐time machine, I retrace the ethnographic task of unwinding technocratic knowledge from those anthropological knowledge practices that critique technocracy. In so doing, I draw attention to special methodological problems—involving the relationship between ethnography, analysis, and reception—in the representation and critique of contemporary knowledge practices.
The Mapuche man who became a woman shaman: Selfhood, gender transgression, and competing cultural norms
Authors: Bacigalupo Ana Mariella
Published: December 2004

Through the life experiences of Marta, a Mapuche male transgendered shaman in Chile, I analyze how selfhood is gendered dynamically by individual desire and competing cultural and religious norms. Marta's unique identity as a divine heterosexual woman is based on a spiritual transformation, her manner of dressing, and her gender performances. It challenges conventional notions of transvestism, transgenderism, and homosexuality linked to sexed bodies. At the same time, Marta's self is shaped and constrained by the normative gender ideologies of the Virgin Mary, shamanic lore, the Mapuche, and dominant Chilean society.
Accountable democracy: Citizens' impact on public decision making in postdictatorship chile
Authors: Paley Julia
Published: December 2004

Using a Santiago, Chile, health group as an ethnographic case study, I propose “accountable democracy” as an alternative normative project to the theory of deliberative democracy outlined by Habermas inBetween Facts and Norms. Accountable democracy has at its center the impact of public‐sphere opinion formation on decision making by officials in elected governments.
Open towns and manipulated indebtedness among agricultural workers in the New South
Authors: Bletzer Keith V.
Published: December 2004

Reselling consumable commodities like food, alcohol, and cigarettes to agricultural workers has long been a strategy of control and indebtedness used by North American labor bosses to manage workers in situations of demanding and risky work. Recent inclusion of crack cocaine among advanced commodities has brought new risks for workers, as it has permitted them a precarious means to enter a once‐restricted resale domain, and it has altered strategies of control and profit by labor contractors by conferring a veneer of independence on workers. Discussion emphasizes an inside view of crack distribution amidst the shifting agencies and counteragencies between labor and management.
Fresh contact in Tamatave, Madagascar: Sex, money, and intergenerational transformation
Authors: Cole Jennifer
Published: December 2004

In this article, I explore practices of transactional sex among young women in contemporary Tamatave, Madagascar. As young men remain suspended in part‐time jobs, young women have been able to embrace the possibilities offered by the informal sexual economy, which links Tamatave to France, RÉunion Island, and beyond as well as creating complex redistributions of resources within Tamatave, shifting the balance of power in gendered and generational relations. Drawing on Karl Mannheim's concept of “fresh contact,” I argue that a focus on the ways in which youthful practice refigures relations between generations works to complicate and nuance recent discussions of youth culture and youth agency.
The Politics of Reproduction in the English Reformation
Authors: FISSELL MARY E.
Published: December 2004

ABSTRACT Practices and beliefs surrounding women's reproductive bodies, in particular those concerning childbirth and reproduction, had religious signi.cance in early modern England and were sites of reform in the Protestant Reformation. In this essay I suggest that the reimagining of women's reproductive bodies was a crucial part of the cultural changes that made England a Protestant nation.
DNA methylation pattern in human zygotes and developing embryos
Authors: Fulka Helena , Mrazek Milan , Tepla Olga , Fulka Josef
Published: December 2004

We report on observations of the global methylation/demethylation pattern of both pronuclei in human zygotes and in early embryos up to the blastocyst stage. Our results demonstrate that in about half of the zygotes examined the paternal chromatin was less methylated than the maternal chromatin. In the other half, both pronuclei exhibited the same intensity of labeling. The nuclei in developing embryos were intensively labeled for up to the four-cell stage; thereafter, a decline of labeling intensity was detected. Remethylation in some nuclei starts in late morulae. Surprisingly, and unlike the mouse, at the blastocyst stage the inner cell mass showed a weaker intensity of labeling than the trophectodermal cells.
Functional significance of the cell volume for detecting sperm membrane changes and predicting freezability in dog semen
Authors: Petrunkina Anna M , Gröpper Barbara , Günzel-Apel Anne-Rose , Töpfer-Petersen Edda
Published: December 2004

Due to the similarity of plasma membrane changes induced by capacitation and cryopreservation, the parameters describing sperm response to capacitating conditions can be used for evaluating the cryopreservation response in many animal systems. In dog sperm, the response of the total sperm population to ionophore treatment has been shown to be an indication of the freezability of semen samples. Another sperm functional characteristic decisive for cryopreservability is cell volume regulation, due to the generation of essential osmotic gradients across the plasma membrane during the freeze-thaw cycles. In the present study, cryopreservation-induced changes in the membrane functional integrity were examined by monitoring the osmotically induced response of cell volume and the response to an ionophore in live cell populations. Cell volume measurements were performed on Percoll-washed suspensions of freshly diluted and frozen-thawed dog spermatozoa. The proportion of live acrosome-reacted cells was evaluated by flow cytometry after incubation under capacitating conditions in the presence of the calcium ionophore, A23187. During freezing-thawing, significant membrane changes occurred related to the disturbance of volume control ability and the loss of a proportion of live acrosome-reacted cells (P < 0.05). There were significant differences between individuals with respect to the degree of functional and structural membrane changes after thawing. Significant correlations were found between acrosomal integrity and functional membrane integrity. When assessed in freshly diluted semen, these parameters correlated with those of frozen-thawed semen samples, pointing to the similarities between mechanisms of cryopreservation-related changes and those mechanisms that mediate changes in membrane permeabilities and in cell volume regulation. The detection of changes in the sperm plasma membrane by monitoring the sperm cell volume represents a simple, rapid and sensitive method to estimate sperm quality after the cryopreservation procedure. The individual variability in response to osmotic stress or to calcium ionophore treatment appears to reflect the subtle differences in the sperm membrane functionality which are crucial for the prediction of cryopreservability.
Reducing agents induce microtubule extrusion in demembranated mammalian spermatozoa
Authors: Kinukawa Masashi , Nagata Masao , Aoki Fugaku
Published: December 2004

To understand the mechanism regulating flagellar bending in spermatozoa, it is important to investigate the regulation of microtubule sliding in the flagellar axoneme. It has been shown that protease treatment following demembranation with Triton X-100 disrupts the connections between microtubules and induces extrusion of microtubules from the flagellar axoneme. This approach enables a direct investigation of the regulation of microtubule sliding; however, the percentage of spermatozoa with protease-induced extrusion was relatively low, probably due to protease digestion of some regulatory motility proteins, as well as proteins connecting the microtubules. In this study, we demonstrate microtubule extrusion in most hamster and mouse demembranated spermatozoa upon treatment with a high concentration of the reducing agents dithiothreitol or 2-mercaptoethanol, without the use of proteases. The extrusion of microtubules occurred when the spermatozoa were treated with concentrations of the reducing agents that were sufficient for the reduction of the disulfide bonds of IgG. These results suggest that the arrangement of the axonemal structures connecting doublet microtubules depends to an important degree on -S-S- bonds. Close observation of the extrusion process using the present method revealed that microtubules were extruded on the same side as that of the curve of the sperm head, and also on the opposite side. Furthermore, we noted that extrusion always started on one side, followed by the other side, but was never initiated on both sides simultaneously.
Protein phosphatase-type 2B is involved in the regulation of the acrosome reaction but not in the temperature-dependent flagellar movement of fowl spermatozoa
Authors: Ashizawa K , Wishart G J , Ranasinghe A R A H , Katayama S , Tsuzuki Y
Published: December 2004

The motility and acrosomal integrity of fowl spermatozoa in TES/NaCl buffer, with or without homogenized inner perivitelline layers (IPVL) prepared from laid fowl eggs, was almost negligible at 40 °C. However, motility became vigorous even at 40 °C when 2 mmol CaCl2/l was added, and the acrosome reaction was also stimulated in the presence, but not in the absence, of IPVL. The presence of deltamethrin or fenvalerate, specific inhibitors of protein phosphatase-type 2B (PP2B), did not permit the restoration of motility at 40 °C but, in the presence of IPVL, these compounds stimulated the acrosome reaction in a dose-dependent manner in the range of 1–1000 nmol/l. These results suggest that IPVL is necessary for the activation of the acrosome reaction in fowl spermatozoa and that Ca2+ plays an important role in the stimulation of motility and acrosomal exocytosis. Furthermore, it appears that the intracellular molecular mechanisms for the regulation of the acrosome reaction of fowl spermatozoa are different from those for the restoration of motility, i.e. protein dephosphorylation by PP2B in the former but not in the latter case.
Follicular, endocrine and behavioural dynamics of the Indian rhinoceros (Rhinoceros unicornis) oestrous cycle
Authors: Stoops Monica A , Pairan Randal D , Roth Terri L
Published: December 2004

Longitudinal ultrasound, behaviour and endocrine evaluations were conducted, over 14 to 18 months, in two young female Indian rhinoceroses (Rhinoceros unicornis) to characterize the oestrous cycle. Both females showed the same pattern of follicular development producing a large follicle (10–12 cm diameter) on one of the ovaries that persisted for 8.5 ± 4.68 days before spontaneously ovulating. Ovulation occurred in all eight cycles monitored in a 6- to 7-year-old female versus 10 out of 14 cycles monitored in a 5- to 6-year-old female. Ultrasound examinations confirmed follicular collapse 48 h following the onset of behavioural oestrus in ovulatory cycles, while anovulatory cycles were associated with the formation of a haemorrhagic follicle. The day of behavioural oestrus corresponded to peak urinary oestrogen conjugate concentrations for each cycle, but anovulatory cycles had lower concentrations on the day of behavioural oestrus compared with ovulatory cycles. A transient increase in urinary progesterone metabolite concentrations was detected 1 day prior to ovulation. Irregular urinary progesterone metabolite profiles followed anovulatory cycles, reflecting varying degrees of follicular luteinization. In an attempt to ensure that a cycle would result in ovulation in the 5- to 6-year-old female, a GnRH treatment was tested during two separate cycles. Administration of GnRH on the day of behavioural oestrus resulted in an increase in urinary luteinizing hormone concentrations 2 h following injection. Regardless, ovulation did not occur in response to treatment. This study provides the first ultrasound data on ovarian activity in the Indian rhinoceros and establishes normal physiologic and behavioural relationships during the oestrous cycle that may facilitate the breeding of this species in captivity.
Animal models of implantation
Authors: Lee Kevin Y , DeMayo Francesco J
Published: December 2004

Implantation is an intricately timed event necessary in the process of viviparous birth that allows mammals to nourish and protect their young during early development. Human implantation begins when the blastocyst both assumes a fixed position in the uterus and establishes a more intimate relationship with the endometrium. Due to the impracticalities of studying implantation in humans, animal models are necessary to decipher the molecular and mechanical events of this process. This review will discuss the differences in implantation between different animal models and describe how these differences can be utilized to investigate discrete implantation stages. In addition, factors that have been shown to be involved in implantation in the human and other various animal models including growth factors, cytokines, modulators of cell adhesion, and developmental factors will be discussed, and examples from each will be given.
Embryonic diapause and its regulation
Authors: Lopes Flavia L , Desmarais Joëlle A , Murphy Bruce D
Published: December 2004

Embryonic diapause, a condition of temporary suspension of development of the mammalian embryo, occurs due to suppression of cell proliferation at the blastocyst stage. It is an evolutionary strategy to ensure the survival of neonates. Obligate diapause occurs in every gestation of some species, while facultative diapause ensues in others, associated with metabolic stress, usually lactation. The onset, maintenance and escape from diapause are regulated by cascades of environmental, hypophyseal, ovarian and uterine mechanisms that vary among species and between the obligate and facultative condition. In the best-known models, the rodents, the uterine environment maintains the embryo in diapause, while estrogens, in combination with growth factors, reinitiate development. Mitotic arrest in the mammalian embryo occurs at the G0 or G1 phase of the cell cycle, and may be due to expression of a specific cell cycle inhibitor. Regulation of proliferation in non- mammalian models of diapause provide clues to orthologous genes whose expression may regulate the reprise of proliferation in the mammalian context.
The Budding Yeast Mei5 and Sae3 Proteins Act Together With Dmc1 During Meiotic Recombination
Authors: Tsubouchi Hideo , Roeder G Shirleen
Published: December 2004

Here we provide evidence that the Mei5 and Sae3 proteins of budding yeast act together with Dmc1, a meiosis-specific, RecA-like recombinase. The mei5 and sae3 mutations reduce sporulation, spore viability, and crossing over to the same extent as dmc1. In all three mutants, these defects are largely suppressed by overproduction of Rad51. In addition, mei5 and sae3, like dmc1, suppress the cell-cycle arrest phenotype of the hop2 mutant. The Mei5, Sae3, and Dmc1 proteins colocalize to foci on meiotic chromosomes, and their localization is mutually dependent. The localization of Rad51 to chromosomes is not affected in either mei5 or sae3. Taken together, these observations suggest that the Mei5 and Sae3 proteins are accessory factors specific to Dmc1. We speculate that Mei5 and Sae3 are necessary for efficient formation of Dmc1-containing nucleoprotein filaments in vivo.
Gene Interactions in Caenorhabditis elegans Define DPY-31 as a Candidate Procollagen C-Proteinase and SQT-3/ROL-4 as Its Predicted Major Target
Authors: Novelli Jacopo , Ahmed Shawn , Hodgkin Jonathan
Published: December 2004

Zinc metalloproteases of the BMP-1/TOLLOID family (also known as astacins) are extracellular enzymes involved in important developmental processes in metazoans. We report the characterization of the Caenorhabditis elegans gene dpy-31, which encodes the first essential astacin metalloprotease identified in this organism. Loss-of-function mutations in dpy-31 result in cuticle defects, abnormal morphology, and embryonic lethality, indicating that dpy-31 is required for formation of the collagenous exoskeleton. DPY-31 is widely expressed in the hypodermal cells, which are responsible for cuticle secretion. We have investigated the dpy-31 function through reversion analysis. While complete reversion can be obtained only by intragenic suppressors, reversion of the Dpy-31 lethal phenotype also can be caused by dominant extragenic suppressors. Nine extragenic suppressors carry mutations in the uniquely essential collagen gene sqt-3, which we show is the same gene as rol-4. Most mutations exhibit the unusual property of exclusively dominant suppression and all affect the sequence of the SQT-3 collagen C terminus. This suggests that DPY-31 is responsible for C-terminal proteolytic processing of collagen trimers and is therefore a structural and functional homolog of vertebrate BMP-1. The results also demonstrate the critical importance of the collagen C-terminal sequence, which is highly conserved among all 49 members of the SQT-3 subfamily.
The Dominant white, Dun and Smoky Color Variants in Chicken Are Associated With Insertion/Deletion Polymorphisms in the PMEL17 GeneSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY636124, AY636125, AY636126, AY636127, AY636128, AY636129.
Authors: Kerje Susanne , Sharma Preety , Gunnarsson Ulrika , Kim Hyun , Bagchi Sonchita , Fredriksson Robert , Schütz Karin , Jensen Per , von Heijne Gunnar , Okimoto Ron , Andersson Leif
Published: December 2004

Dominant white, Dun, and Smoky are alleles at the Dominant white locus, which is one of the major loci affecting plumage color in the domestic chicken. Both Dominant white and Dun inhibit the expression of black eumelanin. Smoky arose in a White Leghorn homozygous for Dominant white and partially restores pigmentation. PMEL17 encodes a melanocyte-specific protein and was identified as a positional candidate gene due to its role in the development of eumelanosomes. Linkage analysis of PMEL17 and Dominant white using a red jungle fowl/White Leghorn intercross revealed no recombination between these loci. Sequence analysis showed that the Dominant white allele was exclusively associated with a 9-bp insertion in exon 10, leading to an insertion of three amino acids in the PMEL17 transmembrane region. Similarly, a deletion of five amino acids in the transmembrane region occurs in the protein encoded by Dun. The Smoky allele shared the 9-bp insertion in exon 10 with Dominant white, as expected from its origin, but also had a deletion of 12 nucleotides in exon 6, eliminating four amino acids from the mature protein. These mutations are, together with the recessive silver mutation in the mouse, the only PMEL17 mutations with phenotypic effects that have been described so far in any species.
Drosophila Klarsicht Has Distinct Subcellular Localization Domains for Nuclear Envelope and Microtubule Localization in the Eye
Authors: Fischer Janice A , Acosta Shelley , Kenny Andrew , Cater Courtney , Robinson Christina , Hook Jay
Published: December 2004

The Drosophila klarsicht (klar) gene is required for developmentally regulated migrations of photoreceptor cell nuclei in the eye. klar encodes a large (∼250 kD) protein with only one recognizable amino acid sequence motif, a KASH (Klar, Anc-1, Syne-1 homology) domain, at its C terminus. It has been proposed that Klar facilitates nuclear migration by linking the nucleus to the microtubule organizing center (MTOC). Here we perform genetic and immunohistochemical experiments that provide a critical test of this model. We analyze mutants in the endogenous klar gene and also flies that express deleted forms of Klar protein from transgenes. We find that the KASH domain of Klar is critical for perinuclear localization and for function. In addition, we find that the N-terminal portion of Klar is also important for function and contains a domain that localizes the protein to microtubules apical to the nucleus. These results provide strong support for a model in which Klar links the nucleus to the MTOC.
Quantitative Trait Loci (QTL) Detection in Multicross Inbred Designs
Authors: Crepieux Sébastien , Lebreton Claude , Servin Bertrand , Charmet Gilles
Published: December 2004

Mapping quantitative trait loci in plants is usually conducted using a population derived from a cross between two inbred lines. The power of such QTL detection and the parameter estimates depend largely on the choice of the two parental lines. Thus, the QTL detected in such populations represent only a small part of the genetic architecture of the trait. In addition, the effects of only two alleles are characterized, which is of limited interest to the breeder, while common pedigree breeding material remains unexploited for QTL mapping. In this study, we extend QTL mapping methodology to a generalized framework, based on a two-step IBD variance component approach, applicable to any type of breeding population obtained from inbred parents. We then investigate with simulated data mimicking conventional breeding programs the influence of different estimates of the IBD values on the power of QTL detection. The proposed method would provide an alternative to the development of specifically designed recombinant populations, by utilizing the genetic variation actually managed by plant breeders. The use of these detected QTL in assisting breeding would thus be facilitated.
Microarray Profiling for Differential Gene Expression in Ovaries and Ovarian Follicles of Pigs Selected for Increased Ovulation Rate
Authors: Caetano Alexandre Rodrigues , Johnson Rodger K , Ford J Joe , Pomp Daniel
Published: December 2004

A unique index line of pigs created by long-term selection ovulates on average 6.7 more ova than its randomly selected control line. Expression profiling experiments were conducted to identify differentially expressed genes in ovarian tissues of the index and control lines during days 2–6 of the follicular phase of the estrous cycle. Fluorescently labeled cDNAs derived from ovary and follicle RNA were cohybridized on microarray slides (n = 90) containing 4608 follicle-derived probes printed in duplicate. Statistical analysis of the resulting ∼1.6 million data points with a mixed-model approach identified 88 and 74 unique probes, representing 71 and 59 unique genes, which are differentially expressed between lines in the ovary and ovarian follicles of different size classes, respectively. These findings indicate that long-term selection for components of litter size has caused significant changes in physiological control of the dynamics of follicular maturation. Genes involved with steroid synthesis, tissue remodeling, and apoptosis, in addition to several genes not previously associated with ovarian physiology or with unknown function, were found to be differentially expressed between lines. This study reveals many potential avenues of investigation for seeking new insights into ovarian physiology and the quantitative genetic control of reproduction.
Conserved Function of Medaka pink-eyed dilution in Melanin Synthesis and Its Divergent Transcriptional Regulation in Gonads Among VertebratesSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY605286 (HNI P-m), AY605287 (Hd-rR P-m), and AY605288 (HNI P-o).
Authors: Fukamachi Shoji , Asakawa Shuichi , Wakamatsu Yuko , Shimizu Nobuyoshi , Mitani Hiroshi , Shima Akihiro
Published: December 2004

Medaka is emerging as a model organism for the study of vertebrate development and genetics, and its effectiveness in forward genetics should prove equal to that of zebrafish. Here, we identify by positional cloning a gene responsible for the medaka i-3 albino mutant. i-3 larvae have weakly tyrosinase-positive cells but lack strongly positive and dendritic cells, suggesting loss of fully differentiated melanophores. The region surrounding the i-3 locus is syntenic to human 19p13, but a BAC clone covering the i-3 locus contained orthologs located at 15q11–13, including OCA2 (P). Medaka P consists of 842 amino acids and shares ∼65% identity with mammalian P proteins. The i-3 mutation is a four-base deletion in exon 13, which causes a frameshift and truncation of the protein. We detected medaka P transcripts in melanin-producing eyeballs and (putative) skin melanophores on embryos and an alternatively spliced form in the non-melanin-producing ovary or oocytes. The mouse p is similarly expressed in gonads, but not alternatively spliced. This is the first isolation of nonmammalian P, the functional mechanism of action of which has not yet been elucidated, even in mammals. Further investigation of the functions of P proteins and the regulation of their expression will provide new insight into body color determination and gene evolution.
A Deficiency Screen for Dominant Suppressors of Telomeric Silencing in Drosophila
Authors: Mason James M , Ransom Joshua , Konev Alexander Y
Published: December 2004

Heterochromatin is a specialized chromatin structure in chromosomal regions associated with repeated DNA sequences and low concentrations of genes. Formation of heterochromatin is determined in large part by enzymes that modify histones and structural proteins that bind to these modified histones in a cooperative fashion. In Drosophila, mutations in genes that encode heterochromatic proteins are often dominant and increase expression of genes placed into heterochromatic positions. To find components of telomeric heterochromatin in Drosophila, we screened a collection of autosomal deficiencies for dominant suppressors of silencing of a transgene at the telomere of chromosome 2L. While many deficiency chromosomes are associated with dominant suppressors, in the cases tested on chromosome 2 the suppressor mapped to the 2L telomere, rather than the deficiency. We infer that background effects may hamper the search for genes that play a role in telomeric heterochromatin formation and that either very few genes participate in this pathway or mutations in these genes are not dominant suppressors of telomeric position effect. The data also suggest that the 2L telomere region plays a major role in telomeric silencing.
Survival signals within the tumour microenvironment suppress drug-induced apoptosis: lessons learned from B lymphomas.
Authors: Taylor S T , Hickman J A , Dive C
Published: December 2004

The suppression of apoptosis is one mechanism by which tumours become drug resitant. Extracellular signals from the germinal centre (GC) of secondary lymphoid tissue can rescue B cells from physiological- and chemotherapy-induced apoptosis. Such survival signals include CD40 receptor ligation, interleukin-4 (IL-4) receptor stimulation and the interaction of the integrin ligand VCAM-1 with its receptor. The GC environment was modelled in vitro by providing B lymphoma cells with these survival signals. JLP119 B lymphoma cells underwent apoptosis after exposure to the topisomerase II inhibitor etoposide and this was dramatically reduced when the cells were cultured in the GC system. CD40 receptor ligation resulted in increased levels of Bcl-XL. Etoposide diminished the binding between Bax and Bcl-XL but this was restored by IL-4 and VCAM-1 triggered signals. These data demonstrate combined effects of three microenvironmental signals on the Bcl-2 family and illustrate the potential importance of such signalling pathways in drug resistance of tumour cells.
Clinical studies of Bcl-2 and treatment benefit in breast cancer patients.
Authors: Daidone M G , Luisi A , Veneroni S , Benini E , Silvestrini R
Published: December 2004

Interest in translational studies aimed at investigating the role of biologic markers in predicting clinical outcome of breast cancer patients and, in particular, response to specific treatments, has progressively increased. Among biologic variables presently under investigation, apoptosis markers, in particular Bcl-2 and Bax expression, are receiving much attention for their relationship with the cellular response to genotoxic damage in experimental tumors. Retrospective, independent studies were carried out by several research groups on about 5000 patients with breast cancer at different stages and with an adequate follow-up. The outcome of separate analyses as a function of treatment generally demonstrated that Bcl-2 overexpression, which correlates with biologic features of a differentiated phenotype (slow proliferation, high steroid receptor levels, absence of p53 and c-erB-2 expression), is associated with a favorable outcome. Such a finding is mainly evident following surgery as well as endocrine treatment. Conversely, no or weak Bcl-2 expression, alone or in association with bax overexpression, appears indicative of a radiation response, and preliminary emerging evidence supports the involvement of such an association of apoptosis-related markers even as predictors of long-term response to neoadjuvant cytotoxic treatment. Although the findings of an involvement of Bcl-2 and Bax as determinants of treatment response should be confirmed within the context of randomized clinical trials, they indicate a combined consideration of proteins that negatively and positively regulate apoptosis in translational studies on the effect of chemical and physical agents at a cellular level.
Serum oestradiol and breast cancer risk.
Authors: Key T J
Published: December 2004

Breast cancer risk is increased by early menarche and late menopause, suggesting that the long duration of exposure of the breasts to the high levels of ovarian steroids in premenopausal women increases risk. Recent prospective studies have shown that postmenopausal women who develop breast cancer have significantly greater prediagnostic serum concentrations of oestradiol than postmenopausal women who remain healthy. Estimation of long-term oestradiol concentrations in premenopausal women is difficult, and few data are available from prospective studies, but these are compatible with the hypothesis that relatively high oestradiol concentrations in premenopausal women are also associated with an increase in breast cancer risk. Women in populations with low breast cancer rates have low serum oestradiol concentrations both before and after the menopause. The serum concentration of oestradiol is probably a major determinant of breast cancer risk, but more data are needed to confirm this and to investigate the possible roles of other sex hormones.
Hormonal interactions in endometrial cancer.
Authors: Emons G , Fleckenstein G , Hinney B , Huschmand A , Heyl W
Published: December 2004

Endometrial cancer (EC) is the most frequent malignant tumor of the female genital tract. Increasing evidence suggests that at least two different types of EC exist. Type I is associated with an endocrine milieu of estrogen predominance. These tumors are of endometrioid histology and develop from endometrial hyperplasia. They have a good prognosis and are sensitive to endocrine manipulation. Type II EC is not associated with a history of unopposed estrogens and develops from the atrophic endometrium of elderly women. They are of serous histology, have a poor prognosis, and do not react to endocrine manipulation. Both types of EC probably differ markedly with regard to the molecular mechanisms of malignant transformation. This article reviews reproductive and lifestyle factors modifying the risk of developing type I EC, including the use of hormonal contraceptives, hormone replacement therapy and tamoxifen. The roles of established and novel therapies for precancerous lesions and for invasive EC in the adjuvant and palliative settings are discussed.
Endometrial cancer: experimental models useful for studies on molecular aspects of endometrial cancer and carcinogenesis.
Authors: Vollmer G
Published: December 2004

There is definitely a need for the development of new drugs for the treatment and cure of endometrial cancer. In addition there are various new drugs or phyto-remedies under development which are intended for use in the treatment and prevention of breast cancer, for the treatment of menopausal symptoms and for hormone replacement therapy. The efficacy of novel drugs targeting steroid receptors in endometrial cancers has to be evaluated and the safety of other endocrine measures on endometrial cancers or on endometrial carcinogenesis has to be assessed. For these experimental purposes five main classes of experimental models are available: spontaneous endometrial tumorigenesis models in inbred animals (Donryu rats, DA/Han rats, BDII/Han rats), inoculation tumors from chunks of tumors (rat EnDA-tumor, human EnCa 101 tumor) or from inoculated tumor cell lines (rat RUCA-I cells, human Ishikawa and ECC-1 cells), developmental estrogenic exposure or chemical carcinogen exposure of CD-1 and ICR mice, transgenic approaches such as mice heterozygous regarding the tumor suppressor gene PTEN (pten(+/-)-mice) and endometrial tumor cell lines cultured under conditions promoting in vivo-like morphology and functions e.g. cell culture on reconstituted basement membrane. Although the number of models is comparatively small, most aspects related to functions of estrogenic or gestagenic substances are assessable, particularly if various experimental models are combined. Whereas models based on human endometrial adenocarcinoma cells are widely used, the properties and advantages of animal-derived models have mainly been ignored so far.
Effects of growth hormone in vitro on the glucose metabolism of fetal rat islet β-cells
Authors: Svensson C
Published: December 2004

This study was undertaken to investigate the effects of growth hormone (GH) on the in vitro maturation of the metabolism of fetal rat islets. For this purpose fetal islets were obtained from 21-day-old fetuses by mild collagenase digestion of the pancreas and cultured in RPMI 1640 supplemented with 10% fetal calf serum. After one day the medium was changed and supplemented with 1% fetal calf serum with or without GH (1 μg/ml, human recombinant) and the islets cultured for another two days. Islets were then studied with regard to insulin secretion, (pro)insulin and total protein biosynthesis, glucose utilization and oxidation, thymidine incorporation, insulin and DNA contents and the contents of mRNAs for either insulin, adenine nucleotide translocator or cytochrome b. In addition, the activities of glucose phosphorylating enzymes and succinate-cytochrome c reductase were measured. Islets treated with GH showed increased insulin secretion in response to glucose, increased rates of glucose oxidation and utilization, increased thymidine incorporation and increased activities of succinate cytochrome c reductase and glucose phosphorylation at high glucose concentrations. There were, however, no changes in (pro)insulin and total protein biosynthesis, contents of insulin and DNA or the contents of any of the mRNAs. These combined data show that fetal β-cells are sensitive to growth hormone with respect to glucose metabolism, insulin release and DNA replication. The increased rates of islet glucose phosphorylation may reflect glucokinase activity and explain part of the increased insulin responsiveness to glucose of the fetal rat β-cell. These observations suggest that GH is of physiological significance for the maturation of the fetal β-cell.
Cell-specific regulation of mRNAs for IGF-I and IGF-binding proteins-4 and -5 in streptozotocin-diabetic rat kidney
Authors: Price G J , Berka J L , Werther G A , Bach L A
Published: December 2004

Streptozotocin (STZ)-induced diabetes in the rat causes early renal enlargement preceded by a transient elevation in IGF-I content and an increase in IGF-I tissue binding. The effects of IGF-I are mainly mediated through the IGF-I receptor (IGF-IR) and modulated by six specific IGF-binding proteins (IGFBPs). We investigated the gene expression of IGF-I, IGF-IR and IGFBPs at a cellular level within the kidney using in situ hybridisation techniques in short-term (7 day) STZ-diabetic, insulin-treated euglycaemic and normal rats. In diabetes, IGFBP-1 mRNA showed markedly increased expression in distal tubules, collecting ducts and thick ascending limbs of Henle (TALs). IGF-I, and IGFBP-4 and -5 mRNAs showed site-specific tubular changes whilst remaining unchanged in other parts of the kidney normally expressing the genes: IGF-I and IGFBP-4 mRNAs were reduced in TALs and proximal tubules respectively; IGFBP-5 mRNA was reduced in most distal tubular cells but strongly expressed in a few of these cells. IGF-IR mRNA and the mRNAs for IGFBP-2, -3 and -6 were unchanged in STZ diabetes. There was no difference between control and insulin-treated kidneys. These complex changes suggest possible involvement of the IGF/IGFBP system in the early stages of diabetic renal hypertrophy.
Comparative in vivo expression of the calcitriol-24-hydroxylase gene in kidney and intestine
Authors: Demers C , Lemay J , Hendy G N , Gascon-Barré M
Published: December 2004

Although the kidney and intestine are among the major organs involved in both the biotransformation and action of vitamin D3, they exhibit very distinct roles in calcium and D3 homeostasis. The aim of the present studies was to investigate the relative in vivo responsiveness of renal and intestinal 1,25(OH)2D3-24-hydroxylase (24-hydroxylase) mRNA levels to calcitriol (1,25(OH)2D3) following acute or chronic 1,25(OH)2D3 exposure using hypocalcemic vitamin D-depleted rats as an experimental model. Intestinal 24-hydroxylase mRNA levels were very responsive to a single i.v. injection of 2·4, 12 or 120nmol 1,25(OH)2D3/kg but in kidney the mRNA levels only increased following exposure to the highest 1,25(OH)2D3 concentration, and exhibited a maximum response only 30% of that in the intestine despite similar tissue uptake of the hormone. To evaluate whether the kidney might preferentially respond to endogenously produced 1,25(OH)2D3, animals received increasing doses of 25(OH)D3. Although the intestinal 24-hydroxylase transcript was highly induced, the renal transcript was unresponsive to 25(OH)D3 treatment despite circulating 1,25(OH)2D3 concentrations of 24 nmol/l. By contrast, intestinal 24-hydroxylase mRNA levels were largely unresponsive to long-term calcitriol administration while the renal transcript, although insensitive to a physiological dose, responded to pharmacological 1,25(OH)2D3 doses. However, when challenged acutely with 1,25(OH)2D3 following chronic exposure, the kidney 24-hydroxylase mRNA levels remained largely unresponsive in contrast to the intestinal transcript which was markedly induced. These data indicate that significant differences exist in the in vivo tissue responsiveness of the 24-hydroxylase mRNA. Indeed, the gene exhibited high intestinal responsiveness to acutely, but not chronically, administered 1,25(OH)2D3, while in the kidney it only responded to high exogenous 1,25(OH)2D3 delivered either acutely or chronically. In addition, these site-specific regulatory mechanisms governing the expression of the 24-hydroxylase gene are independent of the endocrine calcium status and render the kidney relatively resistant to endogenously produced 1,25(OH)2D3.
Somatostatin blocks the potentiation of TRH-induced TSH secretion from perifused pituitary fragments and the change in intracellular calcium concentrations from dispersed pituitary cells elicited by prepro-TRH (PS4) or by tri-iodothyronine
Authors: Roussel J-P , Grazzini E , Astier H
Published: December 2004

TRH and somatostatin (SRIH) are well known to stimulate and to inhibit TSH secretion respectively. However, the mechanisms underlying the effect of SRIH on thyrotrophs are still not understood. We have previously shown in vitro that the TSH response to TRH is potentiated in a Ca2+-dependent fashion through the activation of dihydropyridine (DHP)-sensitive Ca2+ channels by the prepro-TRH (160-169) cryptic peptide (PS4) and tri-iodo-l-thyronine (T3), when the hormone was added shortly before a TRH pulse in order to avoid its genomic effect. Using perifused rat pituitary fragments, the present study has shown that SRIH inhibits, in a dose-dependent manner, the TSH response to physiological concentration of TRH (10 nm) and reverses the Ca2+-dependent potentiation of that response induced either by PS4 or by T3. We have also demonstrated that the inhibition by SRIH of the T3 potentiation of TRH-induced TSH secretion is pertussis toxinsensitive. Our data suggest that SRIH inhibits the PS4 and T3 potentiation of TRH-induced TSH secretion through the inactivation of DHP-sensitive Ca2+ channels.

Using primary cultures of rat anterior pituitary cells and videomicroscopy, we have already demonstrated that TRH, as well as PS4 and T3, are able to increase intracellular Ca2+ concentration ([Ca2+]i) rapidly, in 15 s. Our study has shown that SRIH is able to abolish the acute rise in [Ca2+]i induced either by PS4 or by T3. Since [Ca2+]i responses to PS4 and T3 are also abolished by the DHP nifedipine, our results suggest that [Ca2+]i changes in PS4- or T3-sensitive pituitary cells depend directly or indirectly on the activation of DHP-sensitive Ca2+ channels and that the inhibitory effect of SRIH may be mediated by inactivation of this type of channel.
Recognition of follicle stimulating hormone (alpha-subunit) by a recombinant receptor protein domain coded by an alternately spliced mRNA and expressed in Escherichia coli
Authors: Khan H , Jiang LG , Jayashree GN , Yarney TA , Sairam MR
Published: December 2004

To assess the functional significance of putative proteins encoded by alternately spliced mRNA of the sheep testicular FSH receptor, a short form cDNA comprising of the first four exons (117 residues mature protein) was engineered for expression in Escherichia coli. The expressed protein of molecular mass 15 kDa was purified to homogeneity and verified by reaction with an antibody against a synthetic peptide sequence unique to the amino (N)-terminal region FSH receptor. The purified FSH receptor domain protein bound 125I-labeled hFSH in a ligand blot on polyvinylidine difluoride membranes. Further analyses by slot blot revealed high affinity of the immobilized protein with significant reaction at 10 pmol. As the immobilized receptor protein also reacted with structurally related hormones (125I-labeled LH/125I-labeled human chorionic gonadotropin), we confirmed that interaction most probably occurred via the common alpha-subunit of these glycoprotein hormones. Our results reveal that this N-terminal portion of the FSH receptor contain(s) major site(s) for hormone recognition that could be mediated via the alpha-subunit. A rabbit antibody to the receptor inhibited FSH action in receptor bearing cells, revealing the utility of such recombinant FSH receptor protein(s) for modulation of hormone action.
The long (Gs(alpha)-L) and short (Gs(alpha)-S) variants of the stimulatory guanine nucleotide-binding protein. Do they behave in an identical way?
Authors: Novotny J , Svoboda P
Published: December 2004

The relative proportions and tissue distribution of the long (Gs[alpha]-L) and short (Gs[alpha]-S) variants of the a subunit of the stimulatory G-protein (Gs[alpha]) change under a wide range of metabolic conditions, such as cellular differentiation, ontogenetic development, ageing and various adaptive processes. Although the two variants of Gs(alpha) are generally regarded to be functionally identical, this review summarizes recent experimental support for the non-identical behaviour of these proteins. Similarly, there is no consistent evidence for the functional meaning of these changes as far as regulation of adenylate cyclase activity is concerned. Since it is hard to believe that the complicated scheme of alternative splicing and the energy-consuming synthesis of proteins would be performed for no reason, it is suggested that Gs[alpha] variants might be involved in controlling other effector molecules and processes besides adenylate cyclase and cAMP metabolism. Such an idea is indirectly supported by specific alterations in the Gs[alpha]-L/Gs[alpha]-S ratio under various physiological and pathophysiological conditions.