bluuebunny/crossref_metadata_2025 huggingface dataset:
Consistency in reasoning test scores over time
Authors: Strand Steve
Published: November 2004

Background: UK schools have a long history of using reasoning tests, most frequently of Verbal Reasoning (VR), Non‐Verbal Reasoning (NVR), and to a lesser extent Quantitative Reasoning (QR). Results are used for identifying students' learning needs, for grouping students, for identifying underachievement, and for providing indicators of future academic performance. Despite this widespread use there are little empirical data on the long‐term consistency of VR, QR and NVR as discrete abilities.

Aims: To evaluate and compare the consistency of VR, QR and NVR scores over a 3‐year period, and to explore the influence of the secondary school on pupils' progress in the tests.

Sample: Data were collected on a longitudinal sample of over 10,000 pupils who completed the Cognitive Abilities Test Second Edition in year 6 (age 10+) and year 9 (age 13+), and GCSE public examinations in year 11 (age 15+).

Methods: Correlation coefficients and change scores for individual pupils are calculated. Multilevel modelling is used to determine school effects on reasoning scores and GCSE public examination results.

Results: The results reveal high correlations in scores over time, ranging from .87 for VR to .76 for NVR, but also show around one‐sixth of pupils on the VR test and one‐fifth of pupils on the QR and NVR tests change their scores by 10 or more standard score points. Schools account for only a small part of the total variation in reasoning score, although they account for a much greater proportion of the variation in measures of attainment such as GCSE. School effects on pupils' progress in the reasoning tests between age 10 and age 13 are relatively modest.

Conclusions: Reasoning tests make excellent baseline assessments for secondary schools. Some practical and policy implications for schools are discussed.
A model of aesthetic appreciation and aesthetic judgments
Authors: Leder Helmut , Belke Benno , Oeberst Andries , Augustin Dorothee
Published: November 2004

Although aesthetic experiences are frequent in modern life, there is as of yet no scientifically comprehensive theory that explains what psychologically constitutes such experiences. These experiences are particularly interesting because of their hedonic properties and the possibility to provide self‐rewarding cognitive operations. We shall explain why modern art's large number of individualized styles, innovativeness and conceptuality offer positive aesthetic experiences. Moreover, the challenge of art is mainly driven by a need for understanding. Cognitive challenges of both abstract art and other conceptual, complex and multidimensional stimuli require an extension of previous approaches to empirical aesthetics. We present an information‐processing stage model of aesthetic processing. According to the model, aesthetic experiences involve five stages: perception, explicit classification, implicit classification, cognitive mastering and evaluation. The model differentiates between aesthetic emotion and aesthetic judgments as two types of output.
Linguistic relativism and colour cognition
Authors: Pilling Michael , Davies Ian R.L.
Published: November 2004

Native speakers of two languages (English and Ndonga) were compared on three colour cognition tasks (sorting, triads and visual search) in a test of the linguistic relativity hypothesis (Whorf, 1956). The colour lexicons of these two languages differ because Ndonga has no basic terms for ORANGE, PINK and PURPLE, and stimuli were chosen to exploit this difference. On the sorting task (sorting into similarity‐groups) for each language, nominally similar colours were grouped together more often than nominally dissimilar colours. On the triads task (choosing the most different of three colours), when the most nominally isolated colour differed for the two language‐groups, each group tended to choose their nominal isolate. On the search task (scanning for target colours among distractors), targets were either in a different English category than distractors (cross‐category), or some distractors were in the same English category as distractors (within‐category). The ‘cost’ in speed of having within‐category distractors was much greater for the English than for the Ndonga. Overall, these data suggest that a core universal component is modulated by a small relativist influence. The differences in the visual search task are consistent with language affecting pre‐attentive processes (an indirect language effect) as well as exerting on‐line influences (a direct effect).
What are the implications of the virtual for the human? An analytical ethics of identity in pop culture narratives
Authors: Loren Scott
Published: November 2004

‘What are the implications of the virtual for the human?’ provides a brief analysis of contemporary crises in identity as they are related to authenticity. It does this by way of a primarily psychoanalytical reading of four narratives about artificial beings which are representative
of (if not definitive within) the genre: 2001: A Space Odyssey, AI, Blade Runner, and Frankenstein. By pitting the human against the artificial being, we are presented with certain difficulties in determining alterity and in determining what these very difficulties
represent to us.
‘Much unseen is also here’: John Brinckerhoff Jackson’s new western roadscapes
Authors: Campbell Neil
Published: November 2004

This article examines the legacy of John Brinckerhoff Jackson whose work on American cultural landscapes has had an immense direct and indirect influence on subsequent writers in a number of fields of American Studies. This article examines the western ‘roadscape’ in Jackson’s work as a hybrid, dialogical contact zone that offers a particularly relevant social vision of the New West as mobile and diasporic. In this respect, as in so many other aspects of his work, Jackson was both provocative and ahead of his time.
Cytokine-Induced Activation of Signal Transducer and Activator of Transcription in Photoreceptor Precursors Regulates Rod Differentiation in the Developing Mouse Retina
Authors: Rhee Kun Do , Goureau Olivier , Chen Shiming , Yang Xian-Jie
Published: November 2004

Ciliary neurotrophic factor (CNTF) exhibits multiple biological effects during vertebrate retinogenesis, including regulation of photoreceptor cell differentiation. In the early postnatal mouse retina, CNTF induces rapid and transient phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT3 and the extracellular signal-regulated kinase (ERK). Although both proliferating progenitor cells and postmitotic neurons respond directly to cytokine signals, CNTF elicits distinct phosphorylation patterns of STAT3 and ERK. CNTF stimulation induces low levels of STAT3 phosphorylation in progenitors and differentiated neurons but a robust STAT3 activation among postmitotic photoreceptor precursors expressing the cone-rod homeobox geneCrxand newly differentiated rod photoreceptors. In contrast, CNTF causes preferential phosphorylation of ERK in progenitor cells and photoreceptor precursors. Inhibition of the cytokine receptor gp130 using neutralizing antibodies reveals that gp130 is required for both CNTF-induced STAT3 and ERK phosphorylation. Perturbation of STAT signaling by a STAT inhibitor peptide or a dominant-negative STAT3 mutant causes enhanced production of rod photoreceptors in the absence of exogenous cytokines, whereas inhibiting ERK activation by a MEK (mitogen-activated protein kinase kinase)-specific inhibitor has no effect on rod photoreceptor differentiationin vitro. Furthermore, disrupting the function of epidermal growth factor (EGF) receptors, which modulate rod developmentin vivo, indicates that the EGF family of ligands does not mediate the inhibitory effect of cytokine on rod differentiation. These results demonstrate that cytokine signal transduction is dynamic and heterogeneous in the developing retina, and that endogenous ligand-induced STAT activation in retinal progenitor and/or photoreceptor precursor cells plays an important role in regulating photoreceptor development.
Stimulation of the Posterior Parietal Cortex Interferes with Arm Trajectory Adjustments during the Learning of New Dynamics
Authors: Della-Maggiore Valeria , Malfait Nicole , Ostry David J. , Paus Tomáš
Published: November 2004

Substantial neurophysiological evidence points to the posterior parietal cortex (PPC) as playing a key role in the coordinate transformation necessary for visually guided reaching. Our goal was to examine the role of PPC in the context of learning new dynamics of arm movements. We assessed this possibility by stimulating PPC with transcranial magnetic stimulation (TMS) while subjects learned to make reaching movements with their right hand in a velocity-dependent force field. We reasoned that, if PPC is necessary to adjust the trajectory of the arm as it interacts with a novel mechanical system, interfering with the functioning of PPC would impair adaptation. Single pulses of TMS were applied over the left PPC 40 msec after the onset of movement during adaptation. As a control, another group of subjects was stimulated over the visual cortex. During early stages of learning, the magnitude of the error (measured as the deviation of the hand paths) was similar across groups. By the end of the learning period, however, error magnitudes decreased to baseline levels for controls but remained significantly larger for the group stimulated over PPC. Our findings are consistent with a role of PPC in the adjustment of motor commands necessary for adapting to a novel mechanical environment.
Macrophage Migration Inhibitory Factor: An Intracellular Inhibitor of Angiotensin II-Induced Increases in Neuronal Activity
Authors: Sun Chengwen , Li Hongwei , Leng Lin , Raizada Mohan K. , Bucala Richard , Sumners Colin
Published: November 2004

Angiotensin II (Ang II) elicits Ang II type 1 receptor (AT1-R)-mediated increases in neuronal firing within the hypothalamus and brainstem that are ultimately responsible for physiological actions such as increased blood pressure and fluid intake. Although there is a growing literature on the intracellular mechanisms that mediate the actions of Ang II via AT1-R in neurons, little is known about the mechanisms that diminish or “switch-off” the neuronal chronotropic action of Ang II. In the present study, we identified macrophage migration inhibitory factor (MIF) as an intracellular inhibitor of the actions of Ang II in neurons. The evidence is as follows. First, Ang II, acting via AT1-R, increases the intracellular levels of MIF in neurons cultured from rat hypothalamus and brainstem. Second, elevation of intracellular MIF by Ang II prevents further chronotropic actions of this peptide. Third, intracellular application of exogenous recombinant MIF abolishes the Ang II-induced chronotropic action in neurons. Finally, intracellular application of the MIF peptide fragment MIF-(50-65), which harbors the thiol oxidoreductase property of the MIF molecule, mimics the inhibitory actions of MIF on Ang II-stimulated neuronal firing. Thus, this study is the first to demonstrate the existence of an intracellular negative regulator of Ang II-induced actions in neurons and indicates that MIF may act as a physiological brake for the chronotropic effects of Ang II in rat neurons.
Electrical Coupling among Irregular-Spiking GABAergic Interneurons Expressing Cannabinoid Receptors
Authors: Galarreta Mario , Erdélyi Ferenc , Szabó Gábor , Hestrin Shaul
Published: November 2004

Anatomical studies have shown that the G-protein-coupled cannabinoid receptor-1 (CB1) is selectively expressed in a subset of GABAergic interneurons. It has been proposed that these cells regulate rhythmic activity and play a key role mediating the cognitive actions of marijuana and endogenous cannabinoids. However, the physiology, anatomy, and synaptic connectivity of neocortical CB1-expressing interneurons remain poorly studied. We identified a population of CB1-expressing interneurons in layer II/III in mouse neocortical slices. These cells were multipolar or bitufted, had a widely extending axon, and exhibited a characteristic pattern of irregular spiking (IS) in response to current injection. CB1-expressing-IS (CB1-IS) cells were inhibitory, establishing GABAAreceptor-mediated synapses onto pyramidal cells and other CB1-IS cells. Recently, electrical coupling among other classes of cortical interneurons has been shown to contribute to the generation of rhythmic synchronous activity in the neocortex. We therefore tested whether CB1-IS interneurons are interconnected via electrical synapses using paired recordings. We found that 90% (19 of 21 pairs) of simultaneously recorded pairs of CB1-IS cells were electrically coupled. The average coupling coefficient was ∼6%. Signaling through electrical synapses promoted coordinated firing among CB1-IS cells. Together, our results identify a population of electrically coupled CB1-IS GABAergic interneurons in the neocortex that share a unique morphology and a characteristic pattern of irregular spiking in response to current injection. The synaptic interactions of these cells may play an important role mediating the cognitive actions of cannabinoids and regulating coherent neocortical activity.
Developmental Roles of p73 in Cajal-Retzius Cells and Cortical Patterning
Authors: Meyer Gundela , Socorro Alfredo Cabrera , Garcia Carlos Gustavo Perez , Millan Luis Martinez , Walker Nancy , Caput Daniel
Published: November 2004

To examine the role of the p53 homolog p73 in brain development, we studiedp73-/-,p73+/-,E2F1-/-, andreelermutant mice. p73 in developing brain is expressed in Cajal-Retzius (CR) cells, the cortical hem, and the choroid plexus. p73-expressing CR cells are lost inp73-/-embryos, although Reelin is faintly expressed in the marginal zone. Ectopic neurons in thep73-/-preplate and cortical hem at embryonic day 12 implicate p73 in the early developmental program of the cortex; however, preplate partition and early cortical plate formation are not disturbed. Postnatalp73-/-mice show a mild hypoplasia of the rostral cortex and a severely disrupted architecture of the posterior telencephalon. In the developingp73-/-hippocampus, the most striking abnormality is the absence of the hippocampal fissure, suggesting a role of p73 in cortical folding.p73+/-mice have a less severe cortical phenotype; they display a dorsal shift of the entorhinal cortex and a reduced size of occipital and posterior temporal areas, which acquire entorhinal-like features such as Reelin-positive cells in layer II. CR cells appear unaffected by heterozygosity. We relate the malformations of the posterior pole in p73 mutant mice to alterations of p73 expression in the cortical hem and suggest that p73 forms part of an early signaling network that controls neocortical and archicortical regionalization. In mice deficient for the transcription factor E2F1, a main activator of the TAp73 (transactivating p73) isoform, we find a defect of the caudal cortical architecture resembling thep73+/-phenotype along with reduced TAp73 protein levels and propose that an E2F1-TAp73 dependent pathway is involved in cortical patterning.
Superparamagnetic Iron Oxide-Labeled Schwann Cells and Olfactory Ensheathing Cells Can Be TracedIn Vivoby Magnetic Resonance Imaging and Retain Functional Properties after Transplantation into the CNS
Authors: Dunning Mark D. , Lakatos Andras , Loizou Louiza , Kettunen Mikko , ffrench-Constant Charles , Brindle Kevin M. , Franklin Robin J. M.
Published: November 2004

Schwann cell (SC) and olfactory ensheathing cell (OEC) transplantation has been shown experimentally to promote CNS axonal regeneration and remyelination. To advance this technique into a clinical setting it is important to be able to follow the fates of transplanted cells by noninvasive imaging. Previous studies, using complex modification processes to enable uptake of contrast agents, have shown that cells labeledin vitrowith paramagnetic contrast agents transplanted into rodent CNS can be visualized using magnetic resonance imaging (MRI). Here we show that SCs and OECs efficiently internalize dextran-coated superparamagnetic iron oxide (SPIO) from the culture medium by fluid phase pinocytosis. After transplantation into focal areas of demyelination in adult rat spinal cord both transplanted SPIO-labeled SCs and OECs produce a signal reduction using T2-weighted MRI in anesthetized rats that persists for up to 4 weeks. Although signal reduction was discernable after transplantation of unlabelled cells, this is nevertheless distinguishable from that produced by transplanted labeled cells. The region of signal reduction in SPIO-labeled cell recipients correlates closely with areas of remyelination. Because the retention of functional integrity by labeled cells is paramount, we also show that SPIO-labeled SCs and OECs are able to myelinate normally after transplantation into focal areas of demyelination. These studies demonstrate the feasibility of noninvasive imaging of transplanted SCs and OECs and represent a significant step toward the clinical application of promising experimental approaches.
Transmission Ratio Distortion in Offspring of Mouse Heterozygous Carriers of a (7.18) Robertsonian Translocation
Authors: Underkoffler Lara A , Mitchell Laura E , Abdulali Zaki S , Collins Joelle N , Oakey Rebecca J
Published: November 2004

Transmission ratio distortion (TRD) is defined as a significant departure from expected Mendelian ratios of inheritance of an allele or chromosome. TRD is observed among specific regions of the mouse and human genome and is frequently associated with chromosome rearrangements such as Robertsonian (Rb) chromosomes. We intercrossed mice heterozygous for a (7.18) Rb translocation and genotyped chromosomes 7 and 18 in 1812 individuals, 47% of which were informative for chromosome segregation. We substantiated previous findings that females were less likely than expected to transmit the Rb chromosome to their offspring. Surprisingly, however, we report that heterozygous males transmitted the Rb translocation chromosome significantly more frequently than the acrocentrics. The transmission of the Rb chromosome was not significantly influenced by either the sex of the Rb grandparent or the strain of the Rb.
Detection of Chromosomal Rearrangements Derived From Homeologous Recombination in Four Mapping Populations of Brassica napus L.
Authors: Udall Joshua A , Quijada Pablo A , Osborn Thomas C
Published: November 2004

Genetic maps of Brassica napus were constructed from four segregating populations of doubled haploid lines. Each mapping population had the same male parent and used the same set of RFLP probes, facilitating the construction of a consensus map. Chromosomal rearrangements were identified in each population by molecular marker analysis and were classified as de novo homeologous nonreciprocal transpositions (HNRTs), preexisting HNRTs, and homeologous reciprocal transpositions (HRTs). Ninety-nine de novo HNRTs were identified by the presence of a few lines having duplication of a chromosomal region and loss of the corresponding homeologous region. These de novo HNRTs were more prevalent in one population that had a resynthesized B. napus as a parent. Preexisting HNRTs were identified by fragment duplication or fragment loss in many DH lines due to the segregation of HNRTs preexisting in one of the parents. Nine preexisting HNRTs were identified in the three populations involving natural B. napus parents, which likely originated from previous homeologous exchanges. The male parent had a previously described HRT between N7 and N16, which segregated in each population. These data suggest that chromosomal rearrangements caused by homeologous recombination are widespread in B. napus. The effects of these rearrangements on allelic and phenotypic diversity are discussed.
Role of bilateral adrenalectomy in Cushing's disease
Authors: Favia Gennaro , Boscaro Marco , Lumachi Franco , D'Amico Davide F.
Published: October 2004

Of 206 patients with Cushing's syndrome observed from 1975 through 1991, 144 (69.9%) had pituitary‐dependent Cushing's disease. Of the 110 patients who underwent pituitary surgery, 31 (28%) developed an early recurrence and 23 patients (20%) had a late relapse 1 to 5 years after primary pituitary exploration. We performed a one‐ or two‐step total bilateral adrenalectomy in 43 patients—9 men and 34 (79.4%) women, with an average age of 47.5 years (range 13–58 years). Thirty‐three of these patients had already been treated by previous transsphenoidal surgery or alternatively by external pituitary irradiation over a period of 1 to 10 years prior to adrenal surgery. Thirty‐one patients underwent adrenalectomy by a double lumbar access or left lumbar and right subcostal incisions. In our series of 55 operations, perioperative complications included two splenectomies and two hemorrhages (7.3%). The early mortality rate was 3.6% (two patients). Minor complications consisted of wound infection (13.5%), bronchopneumonia or pneumothorax (four cases) with a 7‐ to 12‐day longer hospital stay. Nelson syndrome occurred in 6 of 41 patients (14.6%). We therefore believe that bilateral adrenalectomy does play a major role in the treatment of patients with pituitary‐dependent Cushing's disease unsuccessfully managed by trans‐sphenoidal surgery. It represents the definitive therapy for those patients in whom hypophysectomy was not able to provide satisfactory control of the disease.
“The” pheochromocytoma: A benign, intra‐adrenal, hypertensive, sporadic unilateral tumor. Does it exist?
Authors: Proye Charles A. G. , Edbg F. R. C. S. , Vix Michel , Jansson Svante , Tisell Lars‐E. , Dralle Hennig , Hiller Wolfgang
Published: October 2004

This study aims to examine the frequency of the pheochromocytoma (pheo), defined as a “benign, intra‐adrenal, hypertensive, sporadic, unilateral tumor.” Three large series amounting to 310 subphrenic chromaffin tumors operated over periods of 17, 23, and 41 years, respectively, have been reviewed. Among those combined 310 pheos, 48 (15.5%) were malignant (i.e., metastatic) and 262 (84.5%) were benign; 42 (13.5%) were ectopic (35% of malignant tumors versus 9.5% of benign tumors); 230 (74.2%) were hypertensive (74% of benign tumors versus 73% of malignant tumors); 29 (9.4%) were bilateral, including 23 patients with a family history; 41 (13.2%) of patients had MEN II type A or B syndrome; and 20 (6.5%) occurred in a phacomatosis setting. Some of the patients had a non‐MEN family history of pheo (n=5), seemingly sporadic hyperparathyroidism (n=4), or other associated neuroendocrine tumor (n=9). Sometimes several of these features were combined. Finally 125 (40.3%) cases fitted the classic description of the tumor, 47.0% at the time of initial presentation and 40.3% at the end of follow‐up. Late occurrence of metastases or metachronous diagnosis of familial disease make lifelong follow‐up mandatory. Genetic studies may be indicated in pheochromocytoma patients.
Fate of untreated benign thyroid nodules: Results of long‐term follow‐up
Authors: Kuma Kanji , Matsuzuka Fumio , Yokozawa Tamotsu , Miyauchi Akira , Sugawara Masahiro
Published: October 2004

The fate of benign thyroid nodules has been unknown because there has been no study in this regard. We re‐examined 134 patients with thyroid nodules who had had benign aspiration biopsy cytology 9 to 11 years ago. The thyroid gland was palpated by the same two thyroidologists throughout the study. Ultrasonography, fine‐needle aspiration biopsy (FNAB), and ultrasound‐guided FNAB were employed to examine the nature of nodules of 9 to 11 years' duration. Patients (n=61) who had nodules difficult to palpate (small nodules), multiple nodules, or cystic nodules with papillomatous proliferation underwent ultrasound‐guided PNAB; patients (n=55) having a distinctly palpable single nodule underwent usual FNAB. None of the patients received any medical or surgical treatment. There were 86 single nodules, 14 multiple nodules, and 34 cystic nodules on the first examination. These benign nodules were reexamined for changes in size and cytology 9 to 11 years later. The most striking finding was a decrease in size or disappearance of the nodule in 42% to 79% of benign nodules. About 92% of nodules remained benign without changing cytologic classification. Only one case (0.9%) previously regarded as benign turned out to be malignant; this nodule grew in size compared with the previous examination. Among single and multiple nodules, 21% to 23% of the nodules increased in size; however, most patients with enlarged nodules (86%) showed the same class 2 cytology as before. Our present study indicates that biopsy‐proved benign thyroid nodules remain benign over a prolonged period. Thus no medical or surgical treatment is required so long as the nodules do not grow.
Proton magnetic resonance and human thyroid neoplasia II: Potential avoidance of surgery for benign follicular neoplasms
Authors: Delbridge Leigh , Lean Cynthia L. , Russell Peter , May George L. , Roman Sandrine , Dowd Susan , Reeve Thomas S. , Mountford Carolyn E.
Published: October 2004

Thyroid cancer is rare, but many thyroidectomies continue to be performed simply to exclude a diagnosis of malignancy. The purpose of this study was to determine the potential financial savings associated with the use of proton magnetic resonance analysis of follicular neoplasms. Proton magnetic resonance spectroscopy was performed on tissue obtained at the time of surgery from 98 consecutive solitary or dominant thyroid nodules. Fine‐needle biopsies were also performed on operative specimens, and the tissues assessed by proton magnetic resonance; these spectra were then compared with those obtained from tissue specimens. An estimate of potential savings was obtained by comparing the magnetic resonance data with the indications for surgery and pathology on all patients having thyroidectomy over a 10‐year period. Proton magnetic resonance spectroscopy was able to distinguish between normal thyroid tissue and invasive thyroid cancer with 100% specificity. Benign follicular adenomas fall into two groups: 44% having a spectral pattern comparable with normal thyroid, and the remaining 56% demonstrating an altered spectral pattern more comparable to the malignant magnetic resonance profile. Proton magnetic resonance spectroscopy on fine‐needle biopsy specimens produced spectra similar to those from tissues from the same patient. From a fine‐needle biopsy specimen, proton magnetic resonance spectroscopy can identify a group of benign follicular adenomas with spectral profiles akin to those of normal thyroid cells, thus avoiding the need for unnecessary surgical excision. The potential savings in one surgical unit alone were over $1 million in 10 years.
Prognostic significance and surgical management of locoregional lymph node metastases in papillary thyroid cancer
Authors: Scheumann Georg F. W. , Gimm Oliver , Wegener Gerd , Hundeshagen H. , Dralle Henning
Published: October 2004

We studied the records of 342 patients with papillary thyroid carcinoma out of a total of 728 thyroid cancer patients treated at the Medical School of Hannover (MHH) from 1972 through 1992. The comprehensive data‐abstracting forms were designed, and the acquired information was coded, stored, maintained, and evaluated by the Clinical Cancer Registry of the MHH. A total of 160 patients (46.8%) initially had lymph node metastases (N1 status). The N status significantly influenced recurrence (p<0.00001) and survival (p<0.00001). Excluding other risk factors developed by univariate and multivariate analysis, such as high age (age >45 years, p<0.001), tumor invasion (T4 tumor, p<0.005), and distant metastases (M1, p<0.001), lymph node metastases remained an independent, highly significant prognostic marker for more aggressive papillary thyroid cancer. N1 status did not influence survival of patients with T4 tumor but did influence those with T1–T3 status (p<0.001). The influence of N1 status remained significant in patients older (p<0.001) and younger (p<0.05) than 45 years of age. Systematic compartmentoriented dissection of lymph node metastases improved survival (p<0.005, T1–T3) and recurrence (p<0.00001, T1–T3) especially in patients with T1–T3 tumors. In conclusion, lymph node metastases with a significant incidence at a young age and male sex had a substantial effect on survival and recurrence especially in those with tumor status T1–T3. Systematic compartment‐oriented dissection of the lymph node metastases results in better survival and a lower recurrence rate.
Diminished expression of the α5β1 integrin (fibronectin receptor) by invasive clones of a human follicular thyroid cancer cell line
Authors: Demeure Michael J. , Doffek Kara M. , Rezaee Mehrdad , Goretzki Peter E. , Wilson Stuart D.
Published: October 2004

Altered adhesion plaques have been observed in transformed cell lines and are associated with enhanced metastatic potential. The prototypical adhesion plaque is formed by α5β1 fibronectin receptors (FnRs) interacting with the cellular actin network. We have found differences in the actin networks of noninvasive (FTC‐133) and invasive (FTC‐236, FTC‐238) clones of a human follicular thyroid cancer cell line. Furthermore, thyroid‐stimulating hormone (TSH) induces stress fibers in FTC‐133. In order to investigate differences in adhesion plaques, expression of fibronectin (FN) and its receptor by these cells was analyzed. For these studies FTC‐133, FTC‐236, and FTC‐238 were cultured in serum‐depleted DME‐H21 medium for 24 hours before the addition of TSH 30 mU/ml. No quantitative differences were noted in FN expression on Western blot in either the conditioned medium or cellular extracts. Western blots and immunohistochemical studies indicated that TSH induced secretion of FN only in FTC‐133. Flow cytometry with an α5 antibody demonstrated a 52% and 45% reduction (p<0.01) in expression of FnR by FTC‐236 and FTC‐238, respectively, compared to FTC‐133; this finding was supported by immunohistochemistry results. TSH treatment did not alter FnR expression. From these studies, we conclude that invasive clones of FTC decrease their expression of FnRs without changing their expression of FN. Furthermore, TSH treatment may promote FN secretion by FTC‐133, although it does not seem to affect FnR or absolute FN expression. The diminished expression of FnR adhesion plaques may enhance metastatic potential in some follicular thyroid cancers.
Parathyroid localization by catheterization of large cervical and mediastinal veins to determine serum concentrations of intact parathyroid hormone
Authors: Nilsson Bengt E. , Tisell Lars‐Erik , Jansson Svante , Zackrisson Bo‐Fredrik , Lindstedt Göran , Lundberg Per‐Arne
Published: October 2004

A success rate of about 90% has been achieved after primary operations for hyperparathyroidism, compared with 60% to 80% in most series of secondary operations. The present reoperative series involved 29 patients who underwent venous catheterization with blood sampling for the determination of intact parathyroid hormone before undergoing repeat parathyroid surgery. Blood samples were taken from the internal jugular veins, innominate veins, and superior caval vein. No attempt was made to perform superselective catheterization of the small neck and mediastinal veins. The reoperations were done by four surgeons who did 1, 2, 13, and 13 of the reoperations, respectively. In all patients, distinct step‐ups in parathyroid hormone concentrations were found. On average, the gradient between the highest and lowest value was about 5. Close to the location of the step‐ups, diseased parathyroid tissue was found in 27 of the patients. In two cases no parathyroid tissue was found, and these patients remained hyperparathyroid postoperatively. They had been treated by the surgeon who did only two of the operations. When the step‐up was observed in the left innominate vein, we could not differentiate mediastinal from low cervical adenomas. No patient developed hypoparathyroidism. To avoid this complication, autotransplantation of diseased parathyroid tissue into the abdominal subcutaneous fat was done in nine patients. No case of recurrent laryngeal nerve paralysis occurred. The introduction of reliable assays for the analysis of parathyroid hormone can make selective catheterization unnecessary when localizing remaining parathyroid glands in patients with persistent hyperparathyroidism.
Primary hyperparathyroidism and the heart: Cardiac abnormalities correlated to clinical and biochemical data
Authors: Längle Friedrich , Abela Claudette , Koller‐Strametz Janette , Mittelböck Martina , Bergler‐Klein Jutta , Stefenelli Thomas , Woloszczuk Wolfgang , Niederle Bruno
Published: October 2004

Comparing patients with primary hyperparathyroidism (PHP) to a normocalcemic control population, those with PHP have a higher incidence of cardiovascular disease and cardiac abnormalities. This study aimed at correlating cardiac findings (valvular and myocardial calcification, myocardial hypertrophy) with clinical data (age, sex, clinical manifestation, nephrolithiasis, nephrocalcinosis, hypertension, skeletal abnormalities, hypercalcemic syndrome) and biochemical data (serum calcium, serum phosphate, serum iPTH level, serum creatinine). A group of 132 consecutive patients with surgically verified PHP (94 women, 38 men; ages 15–86, mean age 57±16 years) were included in this study. Blood chemistry, clinical presentation, radiography, and echocardiography were carried out in all patients for univariate and multivariate analyses of all parameters. There was no statistical correlation between clinical symptoms, biochemical data, and cardiac calcific alterations. Typical skeletal manifestations (osteolysis/subperiostal resorption) and valvular calcifications were significantly correlated to left ventricular hypertrophy (p=0.005). Cardiac abnormalities such as calcific myocardial deposits or mitral and aortic valvular calcifications do not correlate with laboratory findings and clinical presentation at the time of diagnosis. There was no biochemical or clinical variable that could predict the frequency or severity of valvular sclerosis or calcific deposits in the myocardium. However, PHP‐related skeletal abnormalities and valvular calcification were predicting factors for left ventricular hypertrophy, a reversible cardiac manifestation of PHP. Myocardial hypertrophy is more often found with classic symptomatic PHP with osseous abnormalities.
Characteristics of Zinc Transport by Two Bacterial Cation Diffusion Facilitators from
Ralstonia metallidurans
CH34 and
Escherichia coli
Authors: Anton Andreas , Weltrowski Annett , Haney Christopher J. , Franke Sylvia , Grass Gregor , Rensing Christopher , Nies Dietrich H.
Published: October 2004

CzcD from
Ralstonia metallidurans
and ZitB from
Escherichia coli
are prototypes of bacterial members of the cation diffusion facilitator (CDF) protein family. Expression of the
czcD
gene in an
E. coli
mutant strain devoid of
zitB
and the gene for the zinc-transporting P-type ATPase
zntA
rendered this strain more zinc resistant and caused decreased accumulation of zinc. CzcD, purified as an amino-terminal streptavidin-tagged protein, bound Zn
2+
, Co
2+
, Cu
2+
, and Ni
2+
but not Mg
2+
, Mn
2+
, or Cd
2+
, as shown by metal affinity chromatography. Histidine residues were involved in the binding of 2 to 3 mol of Zn
2+
per mol of CzcD. ZitB transported
65
Zn
2+
in the presence of NADH into everted membrane vesicles with an apparent

K
m

of 1.4 μM and a
V
max
of 0.57 nmol of Zn
2+
min
−1
mg of protein
−1
. Conserved amino acyl residues that might be involved in binding and transport of zinc were mutated in CzcD and/or ZitB, and the influence on Zn
2+
resistance was studied. Charged or polar amino acyl residues that were located within or adjacent to membrane-spanning regions of the proteins were essential for the full function of the proteins. Probably, these amino acyl residues constituted a pathway required for export of the heavy metal cations or for import of counter-flowing protons.
Evolutionary Dynamics of Insertion Sequences in
Helicobacter pylori
Authors: Kalia Awdhesh , Mukhopadhyay Asish K. , Dailide Giedrius , Ito Yoshiyki , Azuma Takeshi , Wong Benjamin C. Y. , Berg Douglas E.
Published: October 2004

Prokaryotic insertion sequence (IS) elements behave like parasites in terms of their ability to invade and proliferate in microbial gene pools and like symbionts when they coevolve with their bacterial hosts. Here we investigated the evolutionary history of IS
605
and IS
607
of
Helicobacter pylori
, a genetically diverse gastric pathogen. These elements contain unrelated transposase genes (
orfA
) and also a homolog of the
Salmonella
virulence gene
gipA
(
orfB
). A total of 488 East Asian, Indian, Peruvian, and Spanish isolates were screened, and 18 and 14% of them harbored IS
605
and IS
607
, respectively. IS
605
nucleotide sequence analysis (
n
= 42) revealed geographic subdivisions similar to those of
H. pylori
; the geographic subdivision was blurred, however, due in part to homologous recombination, as indicated by split decomposition and homoplasy tests (homoplasy ratio, 0.56). In contrast, the IS
607
populations (
n
= 44) showed strong geographic subdivisions with less homologous recombination (homoplasy ratio, 0.2). Diversifying selection (ratio of nonsynonymous change to synonymous change, ≫1) was evident in ∼15% of the IS
605 orfA
codons analyzed but not in the IS
607 orfA
codons. Diversifying selection was also evident in ∼2% of the IS
605 orfB
and ∼10% of the IS
607 orfB
codons analyzed. We suggest that the evolution of these elements reflects selection for optimal transposition activity in the case of IS
605 orfA
and for interactions between the OrfB proteins and other cellular constituents that potentially contribute to bacterial fitness. Taken together, similarities in IS elements and
H. pylori
population genetic structures and evidence of adaptive evolution in IS elements suggest that there is coevolution between these elements and their bacterial hosts.
Sequence Organization and Insertion Specificity of the Novel Chimeric IS
Hp609
Transposable Element of
Helicobacter pylori
Authors: Kersulyte Dangeruta , Kalia Awdhesh , Zhang MaoJun , Lee Hae-Kyung , Subramaniam Dharmalingam , Kiuduliene Levute , Chalkauskas Henrikas , Berg Douglas E.
Published: October 2004

Here we describe IS
Hp609
of
Helicobacter pylori
, a new member of the IS
605
mobile element family that is novel and contains two genes whose functions are unknown,
jhp960
and
jhp961
, in addition to homologs of two other
H. pylori
insertion sequence (IS) element genes,
orfA
, which encodes a putative serine recombinase-transposase, and
orfB
, whose homologs in other species are also often annotated as genes that encode transposases. The complete four-gene element was found in 10 to 40% of strains obtained from Africa, India, Europe, and the Americas but in only 1% of East Asian strains. Sequence comparison of 10 representative IS
Hp609
elements revealed higher levels of DNA sequence matches (99%) than those seen in normal chromosomal genes (88 to 98%) or in other IS elements (95 to 97% for IS
605
, IS
606
, and IS
607
) from the same
H. pylori
populations. Sequence analysis suggested that IS
Hp609
can insert at many genomic sites with its left end preferentially next to TAT, with no target specificity for its right end, and without duplicating or deleting target sequences. A deleted form of IS
Hp609
, containing just
jhp960
and
jhp961
and 37 bp of
orfA
, found in reference strain J99, was at the same chromosomal site in 15 to 40% of the strains from many geographic regions but again in only 1% of the East Asian strains. The abundance and sequence homogeneity of IS
Hp609
and of this nonmobile remnant suggested a recent bottleneck and then rapid spread in
H. pylori
populations, possibly selected by the contributions of the elements to bacterial fitness.
Increased Motility ofEscherichia coliby Insertion Sequence Element Integration into the Regulatory Region of theflhDOperon
Authors: Barker Clive S. , Prüß Birgit M. , Matsumura Philip
Published: October 2004

TheflhDoperon is the master operon of the flagellar regulon and a global regulator of metabolism. The genome sequence of theEscherichia coliK-12 strain MG1655 contained an IS1insertion sequence element in the regulatory region of theflhDpromoter. Another stock of MG1655 was obtained from theE. coliGenetic Stock Center. This stock contained isolates which were poorly motile and had no IS1element upstream of theflhDpromoter. From these isolates, motile subpopulations were identified after extended incubation in motility agar. Purified motile derivatives contained an IS5element insertion upstream of theflhDpromoter, and swarm rates were sevenfold higher than that of the original isolate. For a motile derivative, levels offlhDtranscript had increased 2.7-fold, leading to a 32-fold increase infliAtranscript and a 65-fold increase inflhB::luxCDABEexpression from a promoter probe vector. A collection of commonly used lab strains was screened for IS element insertion and motility. Five strains (RP437, YK410, MC1000, W3110, and W2637) contained IS5elements upstream of theflhDpromoter at either of two locations. This correlated with high swarm rates. Four other strains (W1485, FB8, MM294, and RB791) did not contain IS elements in theflhDregulatory region and were poorly motile. Primer extension determined that the transcriptional start site offlhDwas unaltered by the IS element insertions. We suggest that IS element insertion may activate transcription of theflhDoperon by reducing transcriptional repression.
Transfer of the Symbiotic Plasmid of
Rhizobium etli
CFN42 Requires Cointegration with p42a, Which May Be Mediated by Site-Specific Recombination
Authors: Brom Susana , Girard Lourdes , Tun-Garrido Cristina , García-de los Santos Alejandro , Bustos Patricia , González Víctor , Romero David
Published: October 2004

Plasmid p42a from
Rhizobium etli
CFN42 is self-transmissible and indispensable for conjugative transfer of the symbiotic plasmid (pSym). Most pSym transconjugants also inherit p42a. pSym transconjugants that lack p42a always contain recombinant pSyms, which we designated RpSyms*. RpSyms* do not contain some pSym segments and instead have p42a sequences, including the replication and transfer regions. These novel recombinant plasmids are compatible with wild-type pSym, incompatible with p42a, and self-transmissible. The symbiotic features of derivatives simultaneously containing a wild-type pSym and an RpSym* were analyzed. Structural analysis of 10 RpSyms* showed that 7 shared one of the two pSym-p42a junctions. Sequencing of this common junction revealed a 53-bp region that was 90% identical in pSym and p42a, including a 5-bp central region flanked by 9- to 11-bp inverted repeats reminiscent of bacterial and phage attachment sites. A gene encoding an integrase-like protein (
intA
) was localized downstream of the attachment site on p42a. Mutation or the absence of
intA
abolished pSym transfer from a
recA
mutant donor. Complementation with the wild-type
intA
gene restored transfer of pSym. We propose that pSym-p42a cointegration is required for pSym transfer; cointegration may be achieved either through homologous recombination among large reiterated sequences or through IntA-mediated site-specific recombination between the attachment sites. Cointegrates formed through the site-specific system but resolved through RecA-dependent recombination or vice versa generate RpSyms*. A site-specific recombination system for plasmid cointegration is a novel feature of these large plasmids and implies that there is unique regulation which affects the distribution of pSym in nature due to the role of the cointegrate in conjugative transfer.
Decaprenyl Diphosphate Synthesis in
Mycobacterium tuberculosis
Authors: Kaur Devinder , Brennan Patrick J. , Crick Dean C.
Published: October 2004

Z
-prenyl diphosphate synthases catalyze the sequential condensation of isopentenyl diphosphate with allylic diphosphates to synthesize polyprenyl diphosphates. In mycobacteria, these are precursors of decaprenyl phosphate, a molecule which plays a central role in the biosynthesis of essential mycobacterial cell wall components, such as the mycolyl-arabinogalactan-peptidoglycan complex and lipoarabinomannan. Recently, it was demonstrated that open reading frame
Rv2361c
of the
Mycobacterium tuberculosis
H
37
Rv genome encodes a unique prenyl diphosphate synthase (M. C. Schulbach, P. J. Brennan, and D. C. Crick, J. Biol. Chem.
275:
22876-22881, 2000). We have now purified the enzyme to near homogeneity by using an
Escherichia coli
expression system and have shown that the product of this enzyme is decaprenyl diphosphate. Rv2361c has an absolute requirement for divalent cations and an optimal pH range of 7.5 to 8.5, and the activity is stimulated by both detergent and dithiothreitol. The enzyme catalyzes the addition of isopentenyl diphosphate to geranyl diphosphate, neryl diphosphate, ω,
E
,
E
-farnesyl diphosphate, ω,
E
,
Z
-farnesyl diphosphate, or ω,
E
,
E
,
E
-geranylgeranyl diphosphate, with

K
m

values for the allylic substrates of 490, 29, 84, 290, and 40 μM, respectively. The

K
m

value for isopentenyl diphosphate is 89 μM. The catalytic efficiency is greatest when ω,
E
,
Z
-farnesyl diphosphate is used as the allylic acceptor, suggesting that this is the natural substrate in vivo, a conclusion that is supported by previous structural studies of decaprenyl phosphoryl mannose isolated from
M. tuberculosis
. This is the first report of a bacterial
Z
-prenyl diphosphate synthase that preferentially utilizes an allylic diphosphate primer having the α-isoprene unit in the
Z
configuration, indicating that Rv1086 (ω,
E
,
Z
-farnesyl diphosphate synthase) and Rv2361c act sequentially in the biosynthetic pathway that leads to the formation of decaprenyl phosphate in
M. tuberculosis
.
Analysis of the Cytoplasmic Domains ofSalmonellaFlhA and Interactions with Components of the Flagellar Export Machinery
Authors: McMurry Jonathan L. , Van Arnam John S. , Kihara May , Macnab Robert M.
Published: October 2004

Most flagellar proteins are exported via a type III export apparatus which, in part, consists of the membrane proteins FlhA, FlhB, FliO, FliP, FliQ, and FliR and is housed within the membrane-supramembrane ring formed by FliF subunits.SalmonellaFlhA is a 692-residue integral membrane protein with eight predicted transmembrane spans. Its function is not understood, but it is necessary for flagellar export. We have created mutants in which potentially important sequences were deleted. FlhA lacking the amino-terminal sequence prior to the first transmembrane span failed to complement and was dominant negative, suggesting that the sequence is required for function. Similar effects were seen in a variant lacking a highly conserved domain (FHIPEP) within a putative cytoplasmic loop. Scanning deletion analysis of the cytoplasmic domain (FlhAc) demonstrated that substantially all of FlhAc is required for efficient function. Affinity blotting showed that FlhA interacts with several other export apparatus membrane proteins. The implications of these findings are discussed, and a model of FlhA within the export apparatus is presented.
Continuous Control in Bacterial Regulatory Circuits
Authors: Batchelor Eric , Silhavy Thomas J. , Goulian Mark
Published: October 2004

We show that for two well-characterized regulatory circuits in
Escherichia coli
, Tn
10
tetracycline resistance and porin osmoregulation, the transcriptional outputs in individual cells are graded functions of the applied stimuli. These systems are therefore examples of naturally occurring regulatory circuits that exhibit continuous control of transcription. Surprisingly, however, we find that porin osmoregulation is open loop; i.e., the porin expression level does not feed back into the regulatory circuit. This mode of control is particularly interesting for an organism such as
E. coli
, which proliferates in diverse environments, and raises important questions regarding the biologically relevant inputs and outputs for this system.