bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertension and Stroke in Centenarians, Okinawa, Japan
Authors: Arakawa Masashi , Miyake Yoshihiro , Taira Kazuhiko
Published: August 2005

Objective: To investigate the relationship between a history of hypertension, cigarette smoking and alcohol intake and the lifetime prevalence of stroke in the oldest-old population. Design: A cross-sectional study. Subjects: All of the Japanese centenarians in the Okinawa Prefecture (266 men and 1,378 women). Methods: Okinawa Prefectural Government conducted health surveys among all of the centenarians in Okinawa. The variables used for analysis were sex, history of stroke, age at the first diagnosis of stroke, history of hypertension, cigarette smoking and alcohol intake. We used multiple logistic regression analysis taking the history of stroke as the dependent variable. Results: The lifetime prevalence value for stroke was 11.0% in Japanese centenarians. Hypertension was independently associated with an increased lifetime prevalence of stroke (adjusted odds ratio = 2.97 and 95% confidence interval: 2.16–4.08). There was no material relationship between sex, cigarette smoking, oralcohol intake and the prevalence of stroke. When the lifetime prevalence of stroke was divided according to whether stroke had been diagnosed for the first time at the age of 90 years or less or over the age of 90, a significant positive association between hypertension and stroke was more pronounced in centenarians with a diagnosis of stroke at the age of 90 years or less than in those over the age of 90. Conclusions: The findings suggest that hypertension may increase the likelihood of stroke in Japanese centenarians in Okinawa although the association between hypertension and stroke was more pronounced in those having stroke at 90 years or younger.
Patients with Severe Stroke Benefit Most by Interdisciplinary Rehabilitation Team Approach
Authors: Yagura Hajime , Miyai Ichiro , Suzuki Tsunehiko , Yanagihara Takehiko
Published: August 2005

Background: We evaluated the efficacy of a regular interdisciplinary stroke team approach on rehabilitation outcome. Methods: We compared a stroke rehabilitation unit (SRU) with regular interdisciplinary stroke team conferences with general rehabilitation ward (GRW) without such conferences in the same rehabilitation hospital. One hundred and seventy-eight patients within 3 months after stroke were allocated to SRU or GRW, based on bed availability. Main outcome measures were the Functional Independence Measure, Stroke Impairment Assessment Set, length of hospital stay, discharge disposition and cost of hospitalization. Results: The interval between stroke onset and admission to our hospital was significantly longer in the SRU (n = 91) group compared with the GRW group (n = 87, p < 0.05). Although comparable numbers of patients were discharged home (74.7% in the SRU vs. 71.3% in the GRW), significantly more patients (p < 0.0001) with severe disability were discharged home in the SRU group (47.4%) compared with the GRW group (0%). There were no significant differences in the increase in Functional Independence Measure score, Stroke Impairment Assessment Set score,length of hospital stay, or cost. Conclusion: Patients with severe stroke appeared to benefit most from regular interdisciplinary stroke team conferences in the SRU and had an improved discharge disposition.
Agonistic and Antagonistic Action of AP2, Msx2, Pax6, Prox1 and Six3 in the Regulation of Sox2 Expression
Authors: Lengler Johannes , Bittner Tobias , Münster Doris , Gawad Alaa El-Din A. , Graw Jochen
Published: August 2005

Sox2 transcription factor is expressed in neural tissues and sensory epithelia from the early stages of development. Particularly, it is known to activate crystallin gene expression and to be involved in differentiation of lens and neural tissues. However, its place in the signaling cascade is not well understood. Here, we report about the response of its promoter to the presence of other transcription factors, AP2α, Msx2, Pax6, Prox1 and Six3, in a transient reporter gene assay using HEK293 cells as recipient cells. Taking our data together, AP2, Pax6 and PROX1 can activate the Sox2 promoter. Msx2 has an inhibitory effect, whereas Six3 does not affect the Sox2 promoter. These data indicate a common activating cascade at least for AP2, Pax6, Prox1 and Sox2.
Arterial Compliance in Elderly Men with Chronic Kidney Disease
Authors: Yarlagadda Sri G. , Hussain Ambreen , Bravata Dawn M. , Motiwala Shaheen , Peixoto Aldo J.
Published: August 2005

Background/Aim: Chronic kidney disease (CKD) is associated with decreased arterial compliance (AC). The stage of development of impaired arterial function in CKD in relation to loss of glomerular filtration rate (GFR) is not known. This study’s aim was to evaluate the relationship between GFR and AC in patients with CKD. Methods: We recruited 91 men aged ≧60 years with GFR 15–89 ml/min (mean 47 ± 21) to evaluate the relationship between GFR and AC in a cross-sectional study. We measured AC at the brachial artery with an oscillometric device (brachial artery distensibility; BAD). Results: There was no correlation between GFR and BAD (r = 0.08, p = 0.44). When stratified according to CKD stages, all groups showed decreased BAD compared with reference values, and there were no differences among them (one-way ANOVA). Bivariate analyses showed statistically significant correlations between BAD and age (r = –0.23, p = 0.03), antihypertensive drug number (r = 0.27, p = 0.009) and serum hemoglobin (r = 0.24, p = 0.02), but only age and antihypertensive drug number remained significant markers of BAD in a multiple regression model. Conclusion: Older men with CKD have impaired arterial function, but GFR and CKD stage have no relationship to the degree of decrease in brachial artery distensibility.
Thrombospondin-1 and indoleamine 2,3-dioxygenase are major targets of extracellular ATP in human dendritic cells
Authors: Marteau Frédéric , Gonzalez Nathalie Suarez , Communi David , Goldman Michel , Boeynaems Jean-Marie , Communi Didier
Published: August 2005

Extracellular adenosine triphosphate affects the maturation of human monocyte–derived dendritic cells (DCs), mainly by inhibiting T-helper 1 (Th1) cytokines, promoting Th2 cytokines, and modulating the expression of costimulatory molecules. In this study, we report that adenosine triphosphate (ATP) can induce immunosuppression through its action on DCs, defining a new role for extracellular nucleotides. Microarray analysis of ATP-stimulated human DCs revealed inter alia a drastic up-regulation of 2 genes encoding mediators involved in immunosuppression: thrombospondin-1 (TSP-1) and indoleamine 2,3-dioxygenase (IDO). The release of TSP-1 by DCs in response to ATP was confirmed at the protein level by enzyme-linked immunosorbent assay (ELISA), immunodetection, and mass spectrometry analysis, and has an antiproliferative effect on T CD4+ lymphocytes through TSP-1/CD47 interaction. Our pharmacologic data support the involvement of purinergic receptor P2Y11 in this ATP-mediated TSP-1 secretion. We demonstrate also that ATP significantly potentiates the up-regulation of IDO—a negative regulator of T lymphocyte proliferation—and kynurenine production initiated by interferon-γ (IFN-γ) in human DCs.

Thus, extracellular ATP released from damaged cells and previously considered as a danger signal is also a potent regulator of mediators playing key roles in immune tolerance. Consequently, nucleotides' derivatives may be considered as useful tools for DC-based immunotherapies.
Mechanisms of organelle transport and capture along proplatelets during platelet production
Authors: Richardson Jennifer L. , Shivdasani Ramesh A. , Boers Chad , Hartwig John H. , Italiano Joseph E.
Published: August 2005

Megakaryocytes generate platelets by remodeling their cytoplasm into long proplatelet extensions, which serve as assembly lines for platelet production. Platelet packaging and release concludes at the tips of each proplatelet. Essential in this process is the distribution of organelles and platelet-specific granules into the nascent platelets. To investigate the mechanism of delivery of organelles into putative platelets, the distribution and dynamics of organelles/granules was monitored. Individual organelles are sent from the cell body to the proplatelets where they move bidirectionally until they are captured at proplatelet ends. Movement occurs at approximately 0.2 μm/min, but pauses and changes in direction are frequent. At any given time, approximately 30% of organelles/granules are in motion. Actin poisons do not diminish organelle motion, and vesicular structures are intimately associated with the microtubules. Therefore, movement appears to involve microtubule-based forces. Bidirectional organelle movement is conveyed by the bipolar organization of microtubules within the proplatelet, as kinesin-coated beads move bidirectionally on the microtubule arrays of permeabilized proplatelets. Movement of organelles along proplatelets involves 2 mechanisms: organelles travel along microtubules, and the linked microtubules move relative to each other. These studies demonstrate that the components that form platelets are delivered to and assembled de novo along proplatelets.
Restricted mobility of Dnmt1 in preimplantation embryos: implications for epigenetic reprogramming
Authors: Grohmann Maik , Spada Fabio , Schermelleh Lothar , Alenina Natalia , Bader Michael , Cardoso M Cristina , Leonhardt Heinrich
Published: August 2005

Background

Mouse preimplantation development is characterized by both active and passive genomic demethylation. A short isoform of the prevalent maintenance DNA methyltransferase (Dnmt1S) is found in the cytoplasm of preimplantation embryos and transiently enters the nucleus only at the 8-cell stage.

Results

Using GFP fusions we show that both the long and short isoforms of Dnmt1 localize to the nucleus of somatic cells and the cytoplasm of preimplantation embryos and that these subcellular localization properties are independent of phosphorylation. Importantly, photobleaching techniques and salt extraction revealed that Dnmt1S has a very restricted mobility in the cytoplasm, while it is highly mobile in the nucleus of preimplantation embryos.

Conclusion

The restricted mobility of Dnmt1S limits its access to DNA and likely contributes to passive demethylation and epigenetic reprogramming during preimplantationdevelopment.
Exploring cancer register data to find risk factors for recurrence of breast cancer – application of Canonical Correlation Analysis
Authors: Razavi Amir R , Gill Hans , Stål Olle , Sundquist Marie , Thorstenson Sten , Åhlfeldt Hans , Shahsavar Nosrat ,   the South-East Swedish Breast Cancer Study Group
Published: August 2005

Background

A common approach in exploring register data is to find relationships between outcomes and predictors by using multiple regression analysis (MRA). If there is more than one outcome variable, the analysis must then be repeated, and the results combined in some arbitrary fashion. In contrast, Canonical Correlation Analysis (CCA) has the ability to analyze multiple outcomes at the same time.

One essential outcome after breast cancer treatment is recurrence of the disease. It is important to understand the relationship between different predictors and recurrence, including the time interval until recurrence. This study describes the application of CCA to find important predictors for two different outcomes for breast cancer patients, loco-regional recurrence and occurrence of distant metastasis and to decrease the number of variables in the sets of predictors and outcomes without decreasing the predictive strength of the model.

Methods

Data for 637 malignant breast cancer patients admitted in the south-east region of Sweden were analyzed. By using CCA and looking at the structure coefficients (loadings), relationships between tumor specifications and the two outcomes during different time intervals were analyzed and a correlation model was built.

Results

The analysis successfully detected known predictors for breast cancer recurrence during the first two years and distant metastasis 2–4 years after diagnosis. Nottingham Histologic Grading (NHG) was the most important predictor, while age of the patient at the time of diagnosis was not an important predictor.

Conclusion

In cancer registers with high dimensionality, CCA can be used for identifying the importance of risk factors for breast cancer recurrence. This technique can result in a model ready for further processing by data mining methods through reducing the number of variables to important ones.
Removal of power-line interference from the ECG: a review of the subtraction procedure
Authors: Levkov Chavdar , Mihov Georgy , Ivanov Ratcho , Daskalov Ivan , Christov Ivaylo , Dotsinsky Ivan
Published: August 2005

Background

Modern biomedical amplifiers have a very high common mode rejection ratio. Nevertheless, recordings are often contaminated by residual power-line interference. Traditional analogue and digital filters are known to suppress ECG components near to the power-line frequency. Different types of digital notch filters are widely used despite their inherent contradiction: tolerable signal distortion needs a narrow frequency band, which leads to ineffective filtering in cases of larger frequency deviation of the interference. Adaptive filtering introduces unacceptable transient response time, especially after steep and large QRS complexes. Other available techniques such as Fourier transform do not work in real time. The subtraction procedure is found to cope better with this problem.

Method

The subtraction procedure was developed some two decades ago, and almost totally eliminates power-line interference from the ECG signal. This procedure does not affect the signal frequency components around the interfering frequency. Digital filtering is applied on linear segments of the signal to remove the interference components. These interference components are stored and further subtracted from the signal wherever non-linear segments are encountered.

Results

Modifications of the subtraction procedure have been used in thousands of ECG instruments and computer-aided systems. Other work has extended this procedure to almost all possible cases of sampling rate and interference frequency variation. Improved structure of the on-line procedure has worked successfully regardless of the multiplicity between the sampling rate and the interference frequency. Such flexibility is due to the use of specific filter modules.

Conclusion

The subtraction procedure has largely proved advantageous over other methods for power-line interference cancellation in ECG signals.
Reversible Wettability Switch of Large Area TiO2 Films
Authors: Zhou Zhiguo , Li Fuyou , Song Qunliang , Yi Tao , Hou Xiaoyuan , Huang Chunhui
Published: August 2005

On the large area nanoporous TiO2 films with an average pore diameter of 80 nm, reversible wettability switch between high hydrophobicity [contact angle (CA) about 137°] and high hydrophilicity (CA < 10°) was achieved by UV light irradiation and dark storage in alternation.
Lipid Management with Statins in Type 2 Diabetes Mellitus
Authors: Irons Brian K , Kroon Lisa A
Published: August 2005

OBJECTIVE:

To provide an update on lipid management and recent modifications in cholesterol guidelines for use of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), specifically in patients with diabetes.

DATA SOURCES:

Studies and guidelines were identified through a MEDLINE search (1996–April 2005).

STUDY SELECTION AND DATA EXTRACTION:

Studies were selected for review if the primary treatment intervention was a statin, at least 4% of the study population held a diagnosis of diabetes, and diabetes subgroup analysis was available.

DATA SYNTHESIS:

The Heart Protection Study demonstrated an approximately 25% relative risk reduction of a first coronary event in patients with diabetes, a reduction similar to those without diabetes. In subjects with diabetes, a significant reduction in coronary events was noted regardless of the baseline cholesterol level. The Collaborative Atorvastatin Diabetes Study demonstrated a 37% relative risk reduction in the primary prevention of cardiovascular morbidity in patients with diabetes.

CONCLUSIONS:

Based on the current literature, a low-density lipoprotein cholesterol (LDL-C) level <100 mg/dL remains an appropriate goal for patients with diabetes in the absence of established cardiovascular disease. For higher-risk patients, such as those with diabetes and a history of cardiovascular disease, a more stringent LDL-C goal of <70 mg/dL is an option according to current clinical trial evidence. At least a 30–40% reduction in the LDL-C level is advisable when initiating statin therapy.
Estrogen-Induced Increase in the Magnitude of Long-Term Potentiation Occurs Only When the Ratio of NMDA Transmission to AMPA Transmission Is Increased
Authors: Smith Caroline C. , McMahon Lori L.
Published: August 2005

Elevated levels of estradiol enhance learning in mammals, including humans, likely a result of hormone-induced heightened plasticity at CA3-CA1 synapses. The increase in long-term potentiation (LTP) magnitude is considered to be a consequence of the estradiol-induced increase in dendritic spine density and NMDA receptor (NMDAR)-mediated transmission; however, direct evidence linking these changes together is lacking. Alternatively, alterations in GABAergic inhibition or presynaptic release probability could contribute. Here, we show in time course studies using hippocampal slices from estradiol-treated ovariectomized rats that the LTP magnitude is increased only when spine density is increased simultaneously with an increase in NMDAR transmission relative to AMPA receptor (AMPAR) transmission, with no role for alterations in GABAergic inhibition or release probability. With time after hormone treatment, AMPAR transmission gradually increases during the maintained increase in spine density and NMDAR transmission. Eventually, the balance between NMDAR and AMPAR transmission is reestablished, and the LTP magnitude is no longer increased. Blocking genomic estrogen receptors prevents the heightened spine density, NMDAR transmission, and LTP magnitude, suggesting a tight mechanistic coupling between these morphological and functional changes. Thus, we propose that the hormone-induced increase in functional synapse density alone is not sufficient to support heightened plasticity. Rather, estradiol increases LTP via enhancing NMDAR transmission, likely through receptor insertion into newly formed or preexisting synapses. Later, when excitability in the circuit is at its highest and spine density remains elevated, the LTP magnitude is no longer increased, probably as a consequence of the delayed increase in AMPAR transmission that resets the balance between NMDAR and AMPAR transmission.
Conditional Associative Memory for Musical Stimuli in Nonmusicians: Implications for Absolute Pitch
Authors: Bermudez Patrick , Zatorre Robert J.
Published: August 2005

A previous positron emission tomography (PET) study of musicians with and without absolute pitch put forth the hypothesis that the posterior dorsolateral prefrontal cortex is involved in the conditional associative aspect of the identification of a pitch. In the work presented here, we tested this hypothesis by training eight nonmusicians to associate each of four different complex musical sounds (triad chords) with an arbitrary number in a task designed to have limited analogy to absolute-pitch identification. Each subject under-went a functional magnetic resonance imaging scanning procedure both before and after training. Active condition (identification of chords)- control condition (amplitude-matched noise bursts) comparisons for the pretraining scan showed no significant activation maxima. The same comparison for the posttraining scan revealed significant peaks of activation in posterior dorsolateral prefrontal, ventrolateral prefrontal, and parietal areas. A conjunction analysis was performed to show that the posterior dorsolateral prefrontal activity in this study is similar to that observed in the aforementioned PET study. We conclude that the posterior dorsolateral prefrontal cortex is selectively involved in the conditional association aspect of our task, as it is in the attribution of a verbal label to a note by absolute-pitch musicians.
Regulation of Human Recombinant P2X3Receptors by Ecto-Protein Kinase C
Authors: Wirkner Kerstin , Stanchev Doychin , Köles Laszlo , Klebingat Markus , Dihazi Hassan , Flehmig Gesine , Vial Catherine , Evans Richard J. , Fürst Susanna , Mager Peter P. , Eschrich Klaus , Illes Peter
Published: August 2005

The whole-cell patch-clamp technique was used to record current responses to nucleotides and nucleosides in human embryonic kidney HEK293 cells transfected with the human purinergic P2X3receptor. When guanosine 5′-O-(3-thiodiphosphate) was included into the pipette solution, UTP at concentrations that did not alter the holding current facilitated the α,β-methylene ATP (α,β-meATP)-induced current. ATP and GTP, but not UDP or uridine, had an effect similar to that of UTP. Compounds known to activate protein kinase C (PKC) acted like the nucleoside triphosphates investigated, whereas various PKC inhibitors invariably reduced the effects of both PKC activators and UTP. The substitution by Ala of Ser/Thr residues situated within PKC consensus sites of the P2X3receptor ectodomain either abolished (PKC2 and PKC3; T134A, S178A) or did not alter (PKC4 and PKC6; T196A, S269A) the UTP-induced potentiation of the α,β-meATP current. Both the blockade of ecto-protein kinase C activity and the substitution of Thr-134 or Ser-178 by Ala depressed the maximum of the concentration-response curve for α,β-meATP without altering the EC50values. Molecular simulation of the P2X3receptor structure indicated no overlap between assumed nucleotide binding domains and the relevant phosphorylation sites PKC2 and PKC3. α,β-meATP-induced currents through native homomeric P2X3receptors of rat dorsal root ganglia were also facilitated by UTP. In conclusion, it is suggested that low concentrations of endogenous nucleotides in the extracellular space may prime the sensitivity of P2X3receptors toward the effect of subsequently applied (released) higher agonistic concentrations. The priming effect of nucleotides might be attributable to a phosphorylation of PKC sites at the ectodomain of P2X3receptors.
The Oral Antidiabetic Pioglitazone Protects from Neurodegeneration and Amyotrophic Lateral Sclerosis-Like Symptoms in Superoxide Dismutase-G93A Transgenic Mice
Authors: Schütz Burkhard , Reimann Jens , Dumitrescu-Ozimek Lucia , Kappes-Horn Karin , Landreth Gary E. , Schürmann Britta , Zimmer Andreas , Heneka Michael T.
Published: August 2005

Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Because accompanying inflammation may interact with and promote neurodegeneration, anti-inflammatory treatment strategies are being evaluated. Because peroxisome proliferator-activated receptor γ (PPARγ) agonists act as potent anti-inflammatory drugs, we tested whether superoxide dismutase (SOD1)-G93A transgenic mice, a mouse model of ALS, benefit from oral treatment with the PPARγ agonist pioglitazone (Pio). Pio-treated transgenic mice revealed improved muscle strength and body weight, exhibited a delayed disease onset, and survived significantly longer than nontreated SOD1-G93A mice. Quantification of motor neurons of the spinal cord at day 90 revealed complete neuroprotection by Pio, whereas nontreated SOD1-G93A mice had lost 30% of motor neurons. This was paralleled by preservation of the median fiber diameter of the quadriceps muscle, indicating not only morphological but also functional protection of motor neurons by Pio. Activated microglia were significantly reduced at sites of neurodegeneration in Pio-treated SOD1-G93A mice, as were the protein levels of cyclooxygenase 2 and inducible nitric oxide synthase. Interestingly, mRNA levels of the suppressor of cytokine signaling 1 and 3 genes were increased by Pio, whereas both the mRNA and protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected.
Morphine Promotes Rapid, Arrestin-Dependent Endocytosis of μ-Opioid Receptors in Striatal Neurons
Authors: Haberstock-Debic Helena , Kim Kyung-Ah , Yu Y. Joy , von Zastrow Mark
Published: August 2005

Morphine activates μ-opioid receptors (MORs) without promoting their rapid endocytosis in a number of cell types. A previous study suggested that morphine can drive rapid redistribution of MORs in the nucleus accumbens, but it was not possible in thisin vivostudy to identify a specific membrane trafficking pathway affected by morphine, to exclude possible indirect actions of morphine via opiate-regulated neural circuitry, or to define the mechanism of this morphine-dependent regulation. In the present study, we addressed these questions using dissociated primary cultures of rat striatal neurons as a model system. Morphine promoted a rapid redistribution of both endogenous and recombinant MORs within 30 min after drug addition to the culture medium. This effect was mediated by rapid endocytosis and occurred in a cell-autonomous manner, as indicated by its detection in cells plated at low density and in cultures in which depolarization was blocked by tetrodotoxin. Morphine-induced endocytosis of MORs was quantitatively similar to that induced by the enkephalin analogd-Ala2-N-Me-Phe4-Glycol5-enkephalin, and endocytosis induced by both ligands was inhibited by a dominant-negative mutant version of arrestin-3 (β-arrestin-2). These results extend previousin vivoresults and indicate that morphine is indeed capable of driving rapid endocytosis of μ-opioid receptors in an important subset of opiate-responsive CNS neurons. They also suggest a cellular mechanism by which β-arrestins may modulate the physiological effects of morphinein vivo.
Nuclear Pore Complex Function in Saccharomyces cerevisiae Is Influenced by Glycosylation of the Transmembrane Nucleoporin Pom152p
Authors: Belanger Kenneth D , Gupta Amitabha , MacDonald Kristy M , Ott Christina M , Hodge Christine A , Cole Charles M , Davis Laura I
Published: August 2005

The regulated transport of proteins across the nuclear envelope occurs through nuclear pore complexes (NPCs), which are composed of >30 different protein subunits termed nucleoporins. While some nucleoporins are glycosylated, little about the role of glycosylation in NPC activity is understood. We have identified loss-of-function alleles of ALG12, encoding a mannosyltransferase, as suppressors of a temperature-sensitive mutation in the gene encoding the FXFG-nucleoporin NUP1. We observe that nup1Δ cells import nucleophilic proteins more efficiently when ALG12 is absent, suggesting that glycosylation may influence nuclear transport. Conditional nup1 and nup82 mutations are partially suppressed by the glycosylation inhibitor tunicamycin, while nic96 and nup116 alleles are hypersensitive to tunicamycin treatment, further implicating glycosylation in NPC function. Because Pom152p is a glycosylated, transmembrane nucleoporin, we examined genetic interactions between pom152 mutants and nup1Δ. A nup1 deletion is lethal in combination with pom152Δ, as well as with truncations of the N-terminal and transmembrane regions of Pom152p. However, truncations of the N-glycosylated, lumenal domain of Pom152p and pom152 mutants lacking N-linked glycosylation sites are viable in combination with nup1Δ, suppress nup1Δ temperature sensitivity, and partially suppress the nuclear protein import defects associated with the deletion of NUP1. These data provide compelling evidence for a role for glycosylation in influencing NPC function.
Heterozygous Insertions Alter Crossover Distribution but Allow Crossover Interference in Caenorhabditis elegans
Authors: Hammarlund Marc , Davis M Wayne , Nguyen Hung , Dayton Dustin , Jorgensen Erik M
Published: August 2005

The normal distribution of crossover events on meiotic bivalents depends on homolog recognition, alignment, and interference. We developed a method for precisely locating all crossovers on Caenorhabditis elegans chromosomes and demonstrated that wild-type animals have essentially complete interference, with each bivalent receiving one and only one crossover. A physical break in one homolog has previously been shown to disrupt interference, suggesting that some aspect of bivalent structure is required for interference. We measured the distribution of crossovers in animals heterozygous for a large insertion to determine whether a break in sequence homology would have the same effect as a physical break. Insertions disrupt crossing over locally. However, every bivalent still experiences essentially one and only one crossover, suggesting that interference can act across a large gap in homology. Although insertions did not affect crossover number, they did have an effect on crossover distribution. Crossing over was consistently higher on the side of the chromosome bearing the homolog recognition region and lower on the other side of the chromosome. We suggest that nonhomologous sequences cause heterosynapsis, which disrupts crossovers along the distal chromosome, even when those regions contain sequences that could otherwise align. However, because crossovers are not completely eliminated distal to insertions, we propose that alignment can be reestablished after a megabase-scale gap in sequence homology.
TFIID and Spt-Ada-Gcn5-Acetyltransferase Functions Probed by Genome-wide Synthetic Genetic Array Analysis Using a Saccharomyces cerevisiae taf9-ts Allele
Authors: Milgrom Elena , West Robert W , Gao Chen , Shen W-C Winston
Published: August 2005

TAF9 is a TATA-binding protein associated factor (TAF) conserved from yeast to humans and shared by two transcription coactivator complexes, TFIID and SAGA. The essentiality of the TAFs has made it difficult to ascertain their roles in TFIID and SAGA function. Here we performed a genomic synthetic genetic array analysis using a temperature-sensitive allele of TAF9 as a query. Results from this experiment showed that TAF9 interacts genetically with: (1) genes for multiple transcription factor complexes predominantly involving Mediator, chromatin modification/remodeling complexes, and regulators of transcription elongation; (2) virtually all nonessential genes encoding subunits of the SWR-C chromatin-remodeling complex and both TAF9 and SWR-C required for expressing the essential housekeeping gene RPS5; and (3) key genes for cell cycle control at the G1/S transition, as well as genes involved in cell polarity, cell integrity, and protein synthesis, suggesting a link between TAF9 function and cell growth control. We also showed that disruption of SAGA by deletion of SPT20 alters histone-DNA contacts and phosphorylated forms of RNA polymerase II at coding sequences. Our results raise the possibility of an unappreciated role for TAF9 in transcription elongation, perhaps in the context of SAGA, and provide further support for TAF9 involvement in cell cycle progression and growth control.
Saccharomyces cerevisiae Ub-Conjugating Enzyme Ubc4 Binds the Proteasome in the Presence of Translationally Damaged Proteins
Authors: Chuang Show-Mei , Madura Kiran
Published: August 2005

Surveillance mechanisms that monitor protein synthesis can promote rapid elimination of misfolded nascent proteins. We showed that the translation elongation factor eEF1A and the proteasome subunit Rpt1 play a central role in the translocation of nascent-damaged proteins to the proteasome. We show here that multiubiquitinated proteins, and the ubiquitin-conjugating (E2) enzyme Ubc4, are rapidly detected in the proteasome following translational damage. However, Ubc4 levels in the proteasome were reduced significantly in a strain that expressed a mutant Rpt1 subunit. Ubc4 and Ubc5 are functionally redundant E2 enzymes that represent ideal candidates for ubiquitinating damaged nascent proteins because they lack significant substrate specificity, are required for the degradation of bulk, damaged proteins, and contribute to cellular stress-tolerance mechanisms. In agreement with this hypothesis, we determined that ubc4Δ ubc5Δ is exceedingly sensitive to protein translation inhibitors. Collectively, these studies suggest a specific role for Ubc4 and Ubc5 in the degradation of cotranslationally damaged proteins that are targeted to the proteasome.
A Markov Chain Monte Carlo Technique for Identification of Combinations of Allelic Variants Underlying Complex Diseases in Humans
Authors: Favorov Alexander V , Andreewski Timophey V , Sudomoina Marina A , Favorova Olga O , Parmigiani Giovanni , Ochs Michael F
Published: August 2005

In recent years, the number of studies focusing on the genetic basis of common disorders with a complex mode of inheritance, in which multiple genes of small effect are involved, has been steadily increasing. An improved methodology to identify the cumulative contribution of several polymorphous genes would accelerate our understanding of their importance in disease susceptibility and our ability to develop new treatments. A critical bottleneck is the inability of standard statistical approaches, developed for relatively modest predictor sets, to achieve power in the face of the enormous growth in our knowledge of genomics. The inability is due to the combinatorial complexity arising in searches for multiple interacting genes. Similar “curse of dimensionality” problems have arisen in other fields, and Bayesian statistical approaches coupled to Markov chain Monte Carlo (MCMC) techniques have led to significant improvements in understanding. We present here an algorithm, APSampler, for the exploration of potential combinations of allelic variations positively or negatively associated with a disease or with a phenotype. The algorithm relies on the rank comparison of phenotype for individuals with and without specific patterns (i.e., combinations of allelic variants) isolated in genetic backgrounds matched for the remaining significant patterns. It constructs a Markov chain to sample only potentially significant variants, minimizing the potential of large data sets to overwhelm the search. We tested APSampler on a simulated data set and on a case-control MS (multiple sclerosis) study for ethnic Russians. For the simulated data, the algorithm identified all the phenotype-associated allele combinations coded into the data and, for the MS data, it replicated the previously known findings.
Spectral Properties of Pro‐multimodal Imaging Agents Derived from a NIR Dye and a Metal Chelator
Authors: Zhang Zongren , Achilefu Samuel
Published: August 2005

Monomolecular multimodal imaging agents (MOMIAs) are able to provide complementary diagnostic information of a target diseased tissue. We developed a convenient solid‐phase approach to construct two pro‐MOMIAs (before incorporating radiometal) derived from 1,4,7,10‐tetraazacy‐clododecane‐1,4,7,10‐tetraacetic acid (DOTA) and cypate, a near‐infrared (NIR) fluorescent dye analogous to indocyanine green (ICG). The possible interaction between d orbitals of transition metal DOTA complexes or free metals and the p orbitals of cypate chromophore could quench the fluorescence of pro‐MOMIAs. However, we did not observe significant changes in the spectral properties of cypate upon conjugation with DOTA and subsequent chelation with metals. The fluorescence intensity of the chelated and nonmetal‐chelated PRO‐MOMIAs remained fairly the same in dilute 20% aqueous dimethylsulfoxide (DMSO) solution (1 × 10−6M). Significant reduction in the fluorescence intensity of pro‐MOMIAs occurred in the presence of a large excess of metal ions (> 1 molar ratio for indium and 20‐fold for a copper relative to pro‐MOMIA). This study suggests the feasibility of using MOMIAs for combined optical and radioisotope imaging.
Graphical solutions for estimating geosynthetic loads in geosynthetic–soil layered systems on slopes
Authors: Liu C.-N. , Gilbert R. B.
Published: August 2005

This paper presents graphical solutions for estimating geosynthetic loads in geosynthetic–soil layered systems on slopes. The graphical solutions are based on a simple analytical approach that maintains strain compatibility and force equilibrium. The solutions are presented graphically using dimensionless terms that incorporate the loading conditions and material properties. An illustrative example is provided to demonstrate how the graphical solutions are used.
A new algorithm for the rotating-angle, softened-truss model of reinforced concrete elements
Authors: Ji T.
Published: August 2005

Due to a simpler calculation process and better precision, the rotating-angle softened-truss model is often used to predict behaviours of reinforced concrete shell or panel structures. In the current algorithm of the rotating-angle softened-truss model, the calculation process is from strains to stresses, which needs a trial and error procedure. A new algorithm of the rotating-angle softened-truss model is proposed in this paper. The Poisson effect is included in the new algorithm. Its calculation process is from stresses to strains. The trial and error procedure is avoided, which simplifies the calculation process significantly. The reliability of the new algorithm is verified by test data of six panels.
Highly Efficient Non‐Doped Blue Organic Light‐Emitting Diodes Based on Fluorene Derivatives with High Thermal Stability
Authors: Tao S. L. , Peng Z. K. , Zhang X. H. , Wang P. F. , Lee C.‐S. , Lee S.‐T.
Published: August 2005

A new series of blue‐light‐emitting fluorene derivatives have been synthesized and characterized. The fluorene derivatives have high fluorescence yields, good thermal stability, and high glass‐transition temperatures in the range 145–193 °C. Organic light‐emitting diodes (OLEDs) fabricated using the fluorene derivatives as the host emitter show high efficiency (up to 5.3 cd A–1 and 3.0 lm W–1) and bright blue‐light emission (Commission Internationale de L'Eclairage (CIE) coordinates of x = 0.16, y = 0.22). The performance of the non‐doped fluorene‐based devices is among the best fluorescent blue‐light‐emitting OLEDs. The good performance of the present blue OLEDs is considered to derive from: 1) appropriate energy levels of the fluorene derivatives for good carrier injection; 2) good carrier‐transporting properties; and 3) high fluorescence efficiency of the fluorene derivatives. These merits are discussed in terms of the molecular structures.
The effect of ligand type and density on osteoblast adhesion, proliferation, and matrix mineralization
Authors: Harbers Gregory M. , Healy Kevin E.
Published: August 2005

Polystyrene surfaces grafted with a nonfouling interfacial interpenetrating polymer network (IPN) of poly(acrylamide‐co‐ethylene glycol/acrylic acid) [p(AAm‐co‐EG/AAc)] were modified with several peptide ligands adapted from bone sialoprotein (BSP). IPNs were modified with both single ligands and ligand blends to study the correlation between a simple metric, ligand–receptor adhesion strength, and the extent of matrix mineralization for osteoblast like cells (rat calvarial osteoblasts). The ligands studied included RGD cell‐binding [CGGNGEPRGDTYRAY (l‐RGD), CGGEPRGDTYRA (s2‐RGD), CGPRGDTYG (lc‐RGD), cyclic(CGPRGDTYG) (c‐RGD), and CGGPRGDT (s‐RGD)], heparin binding (CGGFHRRIKA), and collagen binding (CGGDGEAG) peptides, with the appropriate controls. Adhesion strength scaled with ligand density (1–20 pmol/cm2) and was dependent on ligand type with the following trend: l‐RGD > s2‐RGD ≈ c‐RGD >> s‐RGD ≈ lc‐RGD >>> FHRRIKA ≈ DGEA. Independent of ligand density, % matrix mineralization varied with ligand type resulting in the following trend: lc‐RGD > s2‐RGD > l‐RGD ≈ c‐RGD >> s‐RGD >>> FHRRIKA. The Tyr (Y) residue immediately following the RGD cell‐binding domain proved to be critical for stable cell proliferation and mineralization, since removal of this residue resulted in erratic cell attachment and mineralization behavior. The minimum BSP sequence necessary for strong adhesion and extensive mineralization was CGGEPRGDTYRA; the minimal sequence suitable for extensive mineralization but lacking strong adhesion was CGPRGDTYG. The cyclic peptide (c‐RGD) had much greater adhesion strength compared to its linear counterpart (lc‐RGD). The calculated characteristic adhesion strength (F70) obtained using a centrifuge adhesion assay proved to be a poor metric for predicting % mineralized area; however, in general, surfaces possessing a F70 > 100g promoted extensive matrix mineralization. Percent mineralization and number of mineralized nodules scaled with number of cells seeded suggesting a critical dependence on the initial number of osteoprogenitors in culture. This study demonstrates matrix mineralization dependence on ligand type, ligand density, and adhesion strength. The high‐throughput character of these surfaces allowed efficient investigation of multiple ligands at multiple densities providing an excellent tool for studying ligand–receptor interactions under normal cell culture conditions with serum present. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Effects of porosity and pore size on in vitro degradation of three‐dimensional porous poly(D,L‐lactide‐co‐glycolide) scaffolds for tissue engineering
Authors: Wu Linbo , Ding Jiandong
Published: August 2005

In vitro degradation of seven three‐dimensional porous scaffolds composed of PLGA85/15, a very useful poly(D,L‐lactide‐co‐glycolide), was performed in phosphate‐buffered saline solution at 37°C up to 26 weeks, and effects of porosity (80–95%) and pore size (50–450 μm) on the degradation of the scaffolds were investigated. A series of quantities were measured during the degradation processes: molecular weight and its distribution of PLGA; compressive strength and modulus; and weight, dimension, and porosity of scaffolds. In all of cases with different pore morphologies, the degradation processes obeyed a three‐stage model. Scaffolds with a higher porosity or a smaller pore size degraded more slowly than and thus outlasted those with a lower porosity or a larger pore size. The effects are both attributed to a wall effect and a surface area effect because the scaffolds with lower porosities or larger pores possess thicker pore walls and smaller surface area, which depress the diffusion of acidic degradation products and thus results in a stronger acid‐catalyzed hydrolysis. This work suggests that, in designing a tissue‐engineering scaffold composed of PLGA and adjusting its degradation rate, the effects of pore morphologies should be taken into consideration in addition to those of chemical composition and condensed state of raw materials. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Elation Laguerre planes of order 16 are ovoidal
Authors: Steinke Günter F.
Published: August 2005

We conduct a computer search for elation Laguerre planes of order 16 and show that each such plane is ovoidal. The search results also confirm the numbers of hyperovals through certain points in the dual translation planes of order 16 given in [15]. © 2005 Wiley Periodicals, Inc. J Combin Designs 14: 313–323, 2006
Renal sexual segment of the ground skink, Scincella laterale (Reptilia, Squamata, Scincidae)
Authors: Sever David M. , Hopkins William A.
Published: August 2005

Mature squamates possess hypertrophied regions of the distal urinary ducts, the renal sexual segment (RSS). The RSS is believed to provide seminal fluid that mixes with sperm and is released into the female cloaca during coitus. This study is the first to describe ultrastructure of the RSS in a lizard collected throughout the active season. The species examined, Scincella laterale, represents the largest family (Scincidae: 1,200 species) of lizards. Although sperm are present in the posterior ductus deferens of male S. laterale throughout the year, an annual spermatogenic cycle occurs that results in spermiation in spring, coinciding with maximum development of the RSS. Female S. laterale may possess stored sperm in vaginal crypts from March–May and large oviductal eggs April–June. Thus, the correlation between mating and RSS activity observed in other squamates is also found in S. laterale. Cytologically, the active RSS consists of columnar cells with numerous apical, electron‐dense secretory vacuoles which are released by an apocrine process. The granules stain positively for proteins with bromphenol blue and react with PAS for neutral carbohydrates. After the mating season the RSS undergoes recrudescence and the electron‐dense granules are replaced by a mucoid secretion that characterizes more proximal portions of the nephric tubules throughout the year. Little variation in ultrastructure of the RSS occurs between S. laterale and Cnemidophorus lemniscatus (Teiidae), the only other lizard in which seasonal variation of the RSS has been studied using similar methods. Females exhibit differentiation similar to that of males in the distal urinary tubules, but to a lesser degree. This is only the second such report for female squamates, and the differentiation of the region in females is proposed to result from adrenal androgens. J. Morphol. Published 2005 Wiley‐Liss, Inc.
Gastrointestinal stromal tumor involving the second and third portion of the duodenum: Treatment by partial duodenectomy and Roux‐en‐Y duodenojejunostomy
Authors: Goh Brian K.P. , Chow Pierce K.H. , Ong Hock‐Soo , Wong Wai‐Keong
Published: August 2005

The optimal surgical procedure for duodenal gastrointestinal tumors (GIST) remains undefined because while surgical resection clearly confers survival advantage, there is little submucosal spread in GIST and lymphatic involvement is rare. Various surgical procedures for duodenal GIST, pancreatoduodenectomy, pancreas‐sparing duodenectomy, segmental duodenectomy, or local resection, have been described depending on the size and exact site of the lesion. In this report, we describe two cases of GIST involving the second and third portion of the duodenum successfully treated by partial duodenectomy with Roux‐en‐Y duodenojejunostomy. This surgical technique is ideal when GIST does not involve the ampulla as it avoids a pancreatoduodenectomy and has not been previously described for the management of this malignancy. J. Surg. Oncol. 2005;91:273–275. © 2005 Wiley‐Liss, Inc.
Personal resources, coping self‐efficacy, and quake exposure as predictors of psychological distress following the 1999 earthquake in Turkey
Authors: Sumer Nebi , Karanci A. Nuray , Berument Sibel Kazak , Gunes Hatice
Published: August 2005

This study examined the predictive power of personal resources (i.e., self‐esteem, optimism, and perceived control), severity of earthquake experience (i.e., material and human loss and perceived threat), and coping self‐efficacy (CSE) on general distress, intrusion, and avoidance symptoms among the survivors of the 1999 Marmara earthquake in Turkey. Specifically, we expected that CSE would mediate the links between personal resources, severity of earthquake experience, and distress. Survivors (N = 336) filled out various measures of earthquake exposure, personal resources, CSE, and distress. Results of the path analyses indicated that personal resources, earthquake experiences, CSE, and gender have direct effects on intrusion and general distress. Personal resources had also an indirect effect on general distress mediated by CSE. Findings were discussed considering the implications for conservation of resources model and social cognitive theory as well as for interventions following natural disasters.