bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuns and Monkeys: Investigating the Behavior of our Oldest Old
Authors: Corr Judith A.
Published: December 2004

The use of nonhuman primates, particularly rhesus macaques (
Macaca mulatta
), as the best model for human physiological and cognitive aging is broadly accepted. Studies employing nonhuman primates to investigate behavioral changes that may occur with increasing age, however, are not common mostly because of the unavailability of appropriate subjects. Recent longitudinal human studies suggest that individual personality might play a large role in aging "successfully" and in the retention of high levels of cognition into old age. As a result of the demographic trend of increasing numbers of aged monkeys and apes in captivity, an opportunity exists to further investigate behavioral aging using the monkey model.
Wilting Weed?
Authors: Davenport R. John
Published: December 2004

COLD SPRING HARBOR, NEW YORK
--Plants might not get gray hair and wrinkles, but they could enhance our understanding of a purported human aging protein. The botanical version of the protein might help clarify the molecule's connection with decrepitude, scientists reported here on 7 October 2004 at the Molecular Genetics of Aging meeting.
Microarrays as a Tool to Investigate the Biology of Aging: A Retrospective and a Look to the Future
Authors: Melov Simon , Hubbard Alan
Published: December 2004

The use of microarrays as a tool to investigate fundamental biological questions has become ubiquitous over the past several years. Microarrays are becoming as common as the polymerase chain reaction or any of the other tools in the molecular biologist's armory. Unlike experiments involving other tools, however, the design and analysis of microarray experiments present some unique problems to molecular biologists, problems with which statisticians have long been familiar. In this overview of microarrays and aging-related research, we will review selected highlights of microarray studies that have been carried out to study aging to date, as well as discuss some of the potential problems that routinely arise during these types of experiments, especially in the context of aging.
Prey for Long Life
Authors: Davenport R. John
Published: December 2004

An inspirational guest on the Sally Jesse Raphael show might tell viewers to make the most of the time they have. Organisms naturally follow that advice, at least according to classical evolutionary theory: To maximize their chances of passing their genes to offspring, they fall apart at different rates, depending on their prospects for survival. But a new study suggests that the simple rule doesn't always apply. Belying the theory, tropical guppies menaced by ravenous predators age more slowly than do guppies from more peaceful waters. The work suggests that scientists need to use more refined theories to describe how evolution shapes life span.
Solving the Energy Crisis
Authors: Davenport R. John
Published: December 2004

Finding enough gas to fill ravenous SUVs isn't the world's only energy crisis. As people age, they lose mitochondria, the cell's power producers. Now, researchers have pegged a signaling molecule that prompts cells to make more of the organelles. The finding could lead researchers to ways of augmenting mitochondrial supplies in the elderly and in people with diseases such as diabetes.
Ironing Out Cell Death
Authors: Leslie Mitch
Published: December 2004

Like a governor giving a pardon, the molecule NF-κB spares cells condemned to death. New research reveals that the protein delivers its stay of execution by enlisting an iron-absorbing protein, which short-circuits a death-promoting pathway. The work could help researchers devise better treatments for conditions in which cells ignore suicide directives, including cancer and rheumatoid arthritis.
Young at Heart
Authors: Davenport R. John
Published: December 2004

Slowing the aging clock keeps the heart ticking strong, according to new work in flies. Insects with a life-stretching genetic alteration maintain robust heart rates and withstand cardiac stress better than do normal insects. The work shows that a mechanism that stalls aging in the entire organism also hinders deterioration of particular tissues.
Mitochondrial Injury: A Hot Spot for Parkinsonism and Parkinson's Disease?
Authors: Giasson Benoit I.
Published: December 2004

The recent identification of genes (
parkin
,
DJ-1
, and
PINK1
) involved in recessive autosomal parkinsonism, and the indications that these proteins may have protective effects on the mitochondria, has led to the reemergence of the notion that mitochondrial dysfunction might play a central role in the etiology of sporadic Parkinson's disease (PD). This idea has previously been supported by biochemical analyses showing reduced mitochondrial activity in PD patients and in animal models of PD generated by the selective inhibition of mitochondria activity. However, the involvement of
DJ-1
or
PINK1
loss of function in classical idiopathic PD, characterized by pathological inclusions composed of aggregated α-synuclein protein, has still not been evaluated. More detailed studies of the possible interactions between parkin, DJ-1, PINK1, and α-synuclein and their effects on mitochondria are needed to more adequately define the biological pathways that may convergently or independently lead to parkinsonism.
Young at Brain
Authors: Leslie Mitch
Published: December 2004

Miniature mice that survive 50% longer than normal boast another advantage over their full-sized counterparts. The puny mice's brains manufacture more new cells, according to new research. This cerebral fecundity might explain why the little rodents retain their memories unusually well.
Ignorance Is Bliss
Authors: Beckman Mary
Published: December 2004

WASHINGTON, D.C.
--Like a living room wall with holes that have been plastered and painted over, cells from people with a premature aging disease can look normal again when the product of the culprit gene is fixed, according to research presented here 6 December 2004 at the American Society for Cell Biology Annual Meeting. The results verify the idea that the faulty protein prevents the normal one from doing its job and provide clues to possible therapy.
Telltale Text
Authors: Leslie Mitch
Published: December 2004

Bad reviews are an occupational hazard for writers, even for Iris Murdoch, whom many critics rank as one of the best 20th century British novelists. But reviewers who lamented the uncharacteristic emptiness and sloppiness of her 1995 novel
Jackson's Dilemma
had noticed more than a literary lapse. Alzheimer's disease was already eroding Murdoch's command of English, according to a new computer analysis of three of her novels.
Once More, With Feeling
Authors: Davenport R. John
Published: December 2004

Shackling a particular receptor protein could sweeten life for diabetic patients, new results suggest. Blocking the molecule, which normally detects sugar-marred proteins, prevents numbness in diabetic mice. Drugs that cripple the receptor might reduce this common diabetes complication.
Expanded Nuclear Roles for IκBs
Authors: Bates Paul W. , Miyamoto Shigeki
Published: December 2004

I kappa B (IκB) was initially identified as a factor that inhibits DNA binding and nuclear translocation of the transcription factor nuclear factor kappa B (NF-κB). Recently, however, IκB family members have demonstrated direct nuclear roles in regulating NF-κB–dependent transcription. Some IκB proteins, including IκBα and IκBβ, can regulate transcription by modulating the concentration of active NF-κB complexes within the nucleus. Others, such as IκBζ and Bcl-3, can directly activate transcription by forming transcriptional complexes at gene promoters. Thus, IκB proteins play important nuclear roles in regulating NF-κB–dependent transcription after stimulation with various extracellular signals.
UV Laser Cross-linking: A Real-Time Assay to Study Dynamic Protein/DNA Interactions During Chromatin Remodeling
Authors: Nagaich Akhilesh K. , Hager Gordon L.
Published: December 2004

We describe the use of laser ultraviolet (UV) cross-linking to study the interaction of transcription factors with in vitro assembled chromatinized DNA templates in real time. Because the laser source delivers a high density of photons in a single ns pulse, the cross-linking reaction is completed in less than 1 microseconds, allowing the investigator to freeze rapid dynamic changes in protein-DNA interactions. Using this approach, we have sampled the dynamic equilibrium of the glucocorticoid receptor (GR) and the chromatin remodeling complex (SWI/SNF) during adenosine triphosphate (ATP)–dependent chromatin remodeling on a chromatinized mouse mammary tumor virus promoter in vitro. UV laser cross-linking shows that the GR and SWI/SNF complex undergoes a periodic binding and displacement event during the process of chromatin remodeling. The assay provides unique information regarding the equilibrium of protein-DNA interactions in real time and can be easily adapted to study the dynamic events in the assembly and disassembly of other multiprotein complexes on chromatin or DNA templates.
The Moving Frontier in Nitric Oxide–Dependent Signaling
Authors: Nathan Carl
Published: December 2004

New discoveries are expanding our view of the role of nitric oxide (NO) in mammalian physiology by revealing new types, amounts, and fates of molecules modified in vivo by NO and its derivatives, as well as the profound augmentation of some of NO’s actions at physiologic levels of O
2
. Investigators have identified a new form of endogenous reversible
N
-nitrosation reactions in vivo, that of proteins; a new class of endogenously nitrated bioactive molecules in vivo, nitro-fatty acids; and the ability of NO-dependent posttranslational modifications to control the half-life and destination of key regulatory proteins.
The Jak-STAT Pathway Stimulated by Interferon γ
Authors: Horvath Curt M.
Published: December 2004

Different cytokines stimulate the Janus kinase (Jak) and signal transducer and activator of transcription (STAT) pathway. Interferon γ (IFN-γ) is a type II interferon that triggers antiviral and adaptive immune responses through a Jak-STAT signaling pathway. These pathways involve a similar paradigm whereby cytokine binding to the receptor activates the Jaks, which phosphorylate STATs leading to their dimerization, translocation to the nucleus, and activation of their transcription factor activity. The animation shows binding of IFN-γ and dimerization of the receptors, activation of Jak1 and Jak2, and phosphorylation of STAT1 leading to dimerization, translocation to the nucleus, and stimulation of target gene transcription.
X-ray microanalysis of airway surface liquid in the mouse
Authors: Kozlova Inna , Nilsson Harriet , Phillipson Mia , Riederer Brigitte , Seidler Ursula , Colledge William H. , Roomans Godfried M.
Published: December 2004

The ionic composition of airway surface liquid (ASL) has been debated, and, in particular for the mouse, a wide range of values has been published. Two techniques were developed to measure the elemental composition of the ASL. X-ray microanalysis of ASL was carried out at low temperature on trachea removed from isoflurane-anesthetized animals and shock-frozen. In the second technique, dextran beads were placed on top of the epithelium of the trachea removed from pentobarbital-anesthetized animals, left to equilibrate with the ASL, dried, and subjected to X-ray microanalysis. Both techniques showed that mouse tracheal ASL has significantly lower concentrations of Na and Cl (∼60–80 mM) than serum. Differences between the two techniques were due to different sampling of mucus. CFTR(−/−) mice had significantly higher concentrations of Na and Cl in their ASL than age-matched controls. Pilocarpine or isoproterenol stimulation significantly reduced the ion concentrations in tracheal ASL. ASL was also collected with the dextran bead method from the nasal cavity in situ in pentobarbital-anesthetized animals. In control animals, the elemental composition of nasal fluid was similar to that of tracheal ASL. Pilocarpine stimulation caused a significant increase in Na, Cl, and K; stimulation with isoproterenol or phenylephrine caused a significant increase only in K. It is concluded that mouse ASL under unstimulated conditions is hypotonic, which may be related to the relative paucity of submucosal glands in the mouse trachea.
Human insulin-like growth factor-IA expression in transgenic mice promotes adenomatous hyperplasia but not pulmonary fibrosis
Authors: Frankel Stephen K. , Moats-Staats Billie M. , Cool Carlyne D. , Wynes Murry W. , Stiles Alan D. , Riches David W. H.
Published: December 2004

Insulin-like growth factor-I (IGF-I) has been implicated in postnatal alveolar development, pulmonary fibrosis, and non-small cell lung cancer. To further investigate the role of IGF-I, we created a line of transgenic mice in which alveolar type II epithelial cells express human IGF-IA under the control of the surfactant protein C promoter. We determined the effect of pulmonary overexpression of human IGF-IA on 1) pulmonary inflammation and fibrosis in response to intratracheal instillation of bleomycin, 2) premalignant pulmonary adenomatous hyperplasia, and 3) adenoma formation. Transgenic expression of human IGF-IA had no effect on baseline gross lung pathology, cellularity of bronchoalveolar lavage, or total lung collagen content. In addition, there were no significant differences between transgenic mice and nontransgenic littermate controls in the development of pulmonary inflammation or pulmonary fibrosis in response to intratracheal bleomycin instillation. However, pulmonary expression of human IGF-IA in older mice (>12 mo) significantly increased the incidence of premalignant adenomatous hyperplastic lesions compared with littermate controls without affecting adenoma formation. These findings suggest that increased expression of human IGF-IA in alveolar air spaces does not affect the development of pulmonary fibrosis but promotes premalignant changes in the alveolar epithelium.
Adenosine A2A-receptor blockade abolishes the roll-off respiratory response to hypoxia in awake lambs
Authors: Koos Brian J. , Kawasaki Yoshikazu , Kim Young-Han , Bohorquez Fanor
Published: December 2004

Adenosine (ADO) receptor antagonists (aminophylline, caffeine) blunt the respiratory roll-off response to hypoxia in the newborn. This study was designed to determine the ADO receptor subtype involved in the respiratory depression. Chronically catheterized lambs of 7–16 days of age breathed via face mask a gas mixture with a fraction of inspired O2 of 0.21 (normoxia) or 0.07 (hypoxia), while being infused intravascularly with 9-cyclopentyl-1,3-dipropylxanthine (DPCPX; ADO A1-receptor antagonist, n = 8), ZM-241385 (ADO A2A-receptor antagonist, n = 7), or vehicle. Ventilation was measured at 20°C by a turbine transducer flowmeter. In normoxia [arterial Po2 (PaO2) of ∼83 Torr], infusion of vehicle did not alter cardiorespiratory measurements, whereas hypoxia (PaO2 of ∼31 Torr, 15 min) elicited biphasic effects on mean arterial pressure (transient increase), heart rate (HR; diminishing tachycardia), and minute ventilation. In the latter, hypoxia increased ventilation to a peak value of ∼2.5 times control within the first 3 min, which was followed by a significant ( P < 0.05) decline to ∼50% of the maximum increment over the subsequent 7 min. ZM-241385 abolished the hypoxic ventilatory roll-off and blunted the rate of rise in HR without affecting mean arterial pressure or rectal temperature responses. In normoxia, DPCPX increased ventilation and mean arterial pressure but did not change HR. Compared with vehicle, DPCPX did not significantly affect cardiorespiratory responses to hypoxemia (PaO2 of ∼31 Torr, 10 min). It is concluded that 1) ADO A2A receptors are critically involved in the ventilatory roll-off and HR responses to hypoxia, and 2) ADO A1 receptors, which are tonically active in cardiorespiratory control in normoxia, appear to have little impact on hypoxic ventilatory depression.
Fatty acid reesterification but not oxidation is increased by oral contraceptive use in women
Authors: Jacobs Kevin A. , Casazza Gretchen A. , Suh Sang-Hoon , Horning Michael A. , Brooks George A.
Published: December 2004

We evaluated the hypothesis that fatty acid reesterification would be increased during rest and exercise in the midluteal menstrual cycle phase and during oral contraceptive use, when ovarian hormone concentrations are high, compared with the early follicular phase. Subjects were eight moderately active, weight-stable, eumenorrheic women (24.8 ± 1.2 yr, peak oxygen consumption = 42.0 ± 2.3 ml·kg−1·min−1) who had not taken oral contraceptives for at least 6 mo. Plasma free fatty acid (FFA) kinetics were assessed in the 3-h postprandial state by continuous infusion of [1-13C]palmitate and [1,1,2,3,3-2H]glycerol during 90 min of rest and 60 min of exercise at 45% and 65% peak oxygen consumption in the early follicular and midluteal menstrual cycle phases and during the inactive- and high-dose phases following 4 mo of oral contraceptive use. Plasma FFA rates of appearance, disappearance, and oxidation increased significantly from rest to exercise with no differences noted between menstrual cycle or oral contraceptive phases or exercise intensities. Compared with either menstrual cycle phase, oral contraceptive use resulted in an increase in plasma-derived fatty acid reesterification and a decrease in the proportion of plasma FFA rate of disappearance that was oxidized at rest and during exercise. Endogenous and exogenous synthetic ovarian hormones do not exert a measurable influence on plasma FFA turnover or oxidation at rest or during moderate-intensity exercise in the 3-h postprandial state when carbohydrate use predominates. The increase in whole body lipolytic rate during exercise noted previously with oral contraceptive use is not matched by an increase in fatty acid oxidation and results in an increase in reesterification. Synthetic ovarian hormones contained in oral contraceptives increase lipolytic rate, but fatty acid oxidation during exercise is determined by exercise intensity and its metabolic and endocrine consequences.
A new and more accurate technique to characterize airway nitric oxide using different breath-hold times
Authors: Shin Hye-Won , Condorelli Peter , George Steven C.
Published: December 2004

Exhaled nitric oxide (NO) arises from both airway and alveolar regions of the lungs, which provides an opportunity to characterize region-specific inflammation. Current methodologies rely on vital capacity breathing maneuvers and controlled exhalation flow rates, which can be difficult to perform, especially for young children and individuals with compromised lung function. In addition, recent theoretical and experimental studies demonstrate that gas-phase axial diffusion of NO has a significant impact on the exhaled NO signal. We have developed a new technique to characterize airway NO, which requires a series of progressively increasing breath-hold times followed by exhalation of only the airway compartment. Using our new technique, we determined values (means ± SE) in healthy adults (20–38 yr, n = 8) for the airway diffusing capacity [4.5 ± 1.6 pl·s−1·parts per billion (ppb)−1], the airway wall concentration (1,340 ± 213 ppb), and the maximum airway wall flux (4,350 ± 811 pl/s). The new technique is simple to perform, and application of this data to simpler models with cylindrical airways and no axial diffusion yields parameters consistent with previous methods. Inclusion of axial diffusion as well as an anatomically correct trumpet-shaped airway geometry results in significant loss of NO from the airways to the alveolar region, profoundly impacting airway NO characterization. In particular, the airway wall concentration is more than an order of magnitude larger than previous estimates in healthy adults and may approach concentrations (∼5 nM) that can influence physiological processes such as smooth muscle tone in disease states such as asthma.
An upper airway resonator model of high-frequency inspiratory sounds in children with sleep-disordered breathing
Authors: Rembold Christopher M. , Suratt Paul M.
Published: December 2004

The goal of this study was to determine how high-frequency inspiratory sounds (HFIS) are generated by sleeping children with obstructive sleep-disordered breathing (OSDB). We hypothesized that HFIS are generated when a high-velocity jet of air, generated by a narrowed upper airway, induces the upper airway to act as a resonating chamber. We tested two predictions of this hypothesis: 1) the upper airway is narrowed in children who make HFIS and 2) the length of the upper airway, calculated from HFIS harmonic intervals, is similar to that calculated from magnetic resonance imaging (MRI) scans. The study was conducted in the setting of a sleep laboratory. Participants included 29 children between 6 and 12 yr of age with adenotonsillar hypertrophy suspected of having OSDB. Minimum cross-sectional airway area and airway long dimensions (lips to larynx or soft palate) were measured in awake children with MRIs. Later that night, sound was recorded with a microphone suspended above their bed while the children underwent polysomnography. Sounds were later analyzed with fast Fourier transforms. We found that sleeping children who generated HFIS had significantly narrower upper airways compared with children who did not make HFIS [minimum airway area 20.5 ± 4.4 vs. 70.9 ± 22.5 mm2(mean ± SE), respectively; P = 0.02]. There was a significant inverse correlation between the log10of the narrowest airway area and the number of HFIS recorded per hour ( r2= 0.55, P < 0.00001). The harmonics characteristics of HFIS predicted that they were generated by sound resonating in chamber whose length was 12.0 ± 0.9 cm, which is similar to the MRI measured distance from the lips to the larynx of 12.8 ± 0.4 cm. In conclusion, these data suggest that children generate HFIS when 1) they have a narrowed upper airway and 2) their upper airway acts as a resonating chamber.
Role of ADP Ribosylation Factor 1 in the Assembly and Secretion of ApoB-100–Containing Lipoproteins
Authors: Asp Lennart , Magnusson Björn , Rutberg Mikael , Li Lu , Borén Jan , Olofsson Sven-Olof
Published: December 2004

Objective—

We investigated the role of ADP ribosylation factor 1 (ARF1) in the assembly of very-low-density lipoproteins (VLDLs).

Methods and Results—

The dominant-negative ARF1 mutant, T31N, decreased the assembly of apoB-100 VLDL 1 (Svedberg floatation units [Sf] 60 to 400) by 80%. The decrease coincided with loss of coatamer I (COPI) from the Golgi apparatus and inhibition of anterograde transport, as demonstrated by time-lapse studies of the vesicular stomatitis virus G protein. The VLDL 1 assembly was also completely inhibited at 15°C. Thus, the antegrade transport is essential for the assembly of VLDL 1. Intracellular localization of
N
-acetylgalactosaminyl transferase 2 indicated that the Golgi apparatus was at least partly intact when the VLDL assembly was inhibited. Transient transfection with phospholipase D 1 increased the assembly of VLDL 1 and VLDL 2 (Sf 20 to 60). Overexpression of ARF1 in stably transfected McA-RH7777 cells increased the secretion of VLDL 2 but not of VLDL 1, which was dependent on the availability of oleic acid. Secretion of VLDL 1 increased with increasing amounts of oleic acid, and VLDL 2 secretion decreased simultaneously.

Conclusions—

Overexpression of ARF1 increased the assembly of VLDL 2 but not of VLDL 1, whose production was dependent on both anterograde transport and the availability of fatty acids.
Glucosamine-Induced Endoplasmic Reticulum Stress Promotes ApoB100 Degradation
Authors: Qiu Wei , Kohen-Avramoglu Rita , Mhapsekar Shailen , Tsai Julie , Austin Richard C. , Adeli Khosrow
Published: December 2004

Objective—

To investigate the role of glucosamine-mediated endoplasmic reticulum (ER) stress and Grp78 (BiP) in the intracellular degradation of apolipoprotein B100 (apoB100) in cultured hepatocytes.

Methods and Results—

Glucosamine treatment (2.5 to 10 mmol/L) of HepG2 cells increased levels of the ER chaperones, 78-kDa glucose-regulated protein (Grp78) and Grp94, in a dose-dependent manner and led to significant decreases in both cellular and secreted apoB100 by up to 97% (
P
<0.01). In contrast, no changes were observed in ER resident (ER60, PTP-1B) or secretory (albumin, apoE) control proteins. Glucosamine-induced apoB degradation was similarly observed in primary hamster hepatocytes and McA-RH7777 cells. Glucosamine treatment led to reduced tranlocational efficiency of apoB100 in the ER and enhanced its ubiquitination and proteasomal degradation. Adenoviral overexpression of Grp78 also led to significantly decreased levels of newly synthesized apoB100 in a dose-dependent manner (
P
<0.01). Grp78-induced downregulation of apoB100 was sensitive to inhibition by the proteasome inhibitor, lactacystin, but not lysosomal protease inhibitors, E64 and leupeptin, suggesting that overexpression of Grp78 selectively induced proteasomal degradation of apoB100.

Conclusion—

These findings suggest that binding and retention by Grp78 may play a critical role in proteasomal targeting and the ER quality-control of misfolded apoB. Interaction with core lipoprotein lipids may facilitate apoB transport out of the ER by reducing Grp78-mediated ER retention.
Paradoxical Effects of Statins on Aortic Valve Myofibroblasts and Osteoblasts
Authors: Wu Bing , Elmariah Sammy , Kaplan Frederick S. , Cheng Guanjun , Mohler Emile R.
Published: December 2004

Objectives—

We evaluated the effects of statins on aortic valve myofibroblasts (AVMFs) and osteoblast calcification in vitro.

Methods and Results—

Cultured porcine AVMFs and M2–10B4 cells were treated with simvastatin and pravastatin. Mevalonate, a 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase metabolite, was added in parallel experiments. Manumycin A, which inhibits protein prenylation, was added to cultures in the absence of statins. Calcification was assessed by counting the number of calcific nodules formed and measuring alkaline phosphatase activity (APA). Statins inhibited calcific nodule formation (
P
<0.01) and APA (
P
<0.01) in AVMFs. Mevalonate reversed the statin effect on nodule formation (
P
<0.05) and APA (
P
<0.01). Manumycin A had no effect on either parameter. M2–10B4 cells treated with simvastatin formed more calcific nodules compared with controls (
P
<0.01), although pravastatin had no effect. Both statins, however, resulted in increased APA in M2–10B4 cells (
P
<0.01). Mevalonate had no impact on nodule numbers or APA in M2–10B4 cells.

Conclusions—

Statins inhibit calcification in AVMFs by inhibiting the cholesterol biosynthetic pathway, independent of protein prenylation, but paradoxically stimulate bone cell calcification. Because 15% of patients with end-stage valvular heart disease exhibit mature bone in their aortic valves, statins may differentially regulate calcification within a valve, limiting dystrophic calcification but promoting ossification of formed bone.
Core Protein of Hepatitis C Virus Induces Cardiomyopathy
Authors: Omura Takashi , Yoshiyama Minoru , Hayashi Tetsuya , Nishiguchi Shuhei , Kaito Masahiko , Horiike Shinichiro , Fukuda Katsuhiko , Inamoto Sakiko , Kitaura Yasushi , Nakamura Yasuhiro , Teragaki Masakazu , Tokuhisa Takeshi , Iwao Hiroshi , Takeuchi Kazuhide , Yoshikawa Junichi
Published: December 2004

Hepatitis C virus (HCV) has been reported to be associated with cardiomyopathy. However, the mechanism of cardiomyopathy in chronic HCV infection is still unclear. Therefore, we investigate the development of cardiomyopathy in mice transgenic for the HCV-core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction assessed by Doppler echocardiography. Histologically, hypertrophy of cardiomyocytes, cardiac fibrosis, disarray and scarcity of myofibrils, vacuolization and deformity of nuclei, myofibrillar lysis, streaming of Z-bands, and an increased number of bizarre-shaped mitochondria were found in HCV-core transgenic mice. These histological changes are just consistent with cardiomyopathy. In conclusion, the HCV-core protein directly plays an important role in the development of cardiomyopathy.
Magnetic Resonance Imaging Criteria for Thrombolysis in Acute Cerebral Infarct
Authors: Hjort N. , Butcher K. , Davis S.M. , Kidwell C.S. , Koroshetz W.J. , Röther J. , Schellinger P.D. , Warach S. , Østergaard L.
Published: December 2004

Background and Purpose—

Magnetic resonance imaging (MRI) selection of stroke patients eligible for thrombolytic therapy is an emerging application. Although the efficacy of therapy within 3 hours after onset of symptoms with intravenous (IV) tissue plasminogen activator (tPA) has been proven for patients selected with computed tomography (CT), no randomized, double-blinded MRI trial has been published yet.

Summary of Review—

MRI screening of acute stroke patients before thrombolytic therapy is performed in some cerebrovascular centers. In contrast to the CT trials, MRI pilot studies demonstrate benefit of therapy up to 6 hours after onset of symptoms. This article reviews the literature that has lead to current controlled MRI-based thrombolysis trials. We examined the MRI criteria applied in 5 stroke centers. Along with the personal views of clinicians at these centers, the survey reveals a variety of clinical and MRI technical aspects that must be further investigated: the therapeutic consequence of microbleeds, the use of magnetic resonance angiography, dynamic time windows, and others.

Conclusion—

MRI is an established application in acute evaluation of stroke patients and may suit as a brain clock, replacing the currently used epidemiological time clock when deciding whether to initiate thrombolytic therapy. MRI criteria for thrombolytic therapy are applied in some cerebrovascular centers, but the results of ongoing clinical trials must be awaited before it is possible to reach consensus.
Anxiety and Outcome Predictions
Authors: Shepperd James A. , Grace Jodi , Cole Laura J. , Klein Cynthia
Published: December 2004

Research shows that people display a downward shift in their predictions in anticipation of performance and feedback. The authors used a misattribution paradigm to explore whether anxiety serves as a signal for predictions. Participants (N = 108) anticipating results from an important test either immediately or in a few days were or were not encouraged to attribute any arousal they experienced to coffee they consumed earlier. Consistent with predictions, participants encouraged to attribute their arousal to the coffee were optimistic in their predictions even when anticipating immediate test feedback. In addition, the more participants attributed their arousal to the coffee, the more optimistic they were in their predictions. Ancillary analyses suggest that anxiety can be a cause rather than a consequence of less optimistic predictions.
Self-Esteem and Affect as Information
Authors: Harber Kent D.
Published: December 2004

This research tests whether people with high self-esteem are more informed by their emotions than are people with low self-esteem. In Study 1, participants listened to a series of disturbing baby cries, rated how much distress these cries conveyed, and reported their own emotional reactions to the cries. As predicted, the relation between participants’ emotional reactions and their cry ratings was strongest at higher levels of self-esteem. In Study 2, self-esteem again determined how strongly participants’ own emotional reactions influenced their baby cry ratings, even though esteem was measured weeks before the experiment and even after controlling for social desirability. Study 3 manipulated self-regard and showed that the correlation between participants’ emotional reactions and their cry ratings was strong for high-regard participants, moderate for control participants, and weak for low-regard participants. These results suggest that self-esteem serves to validate the informational value of feelings.
Gender Differences in Unrealistic Optimism About Marriage and Divorce: Are Men More Optimistic and Women More Realistic?
Authors: Lin Ying-Ching , Raghubir Priya
Published: December 2004

Two studies (n = 497) examine gender differences in “unrealistic optimism” in beliefs of marriage using a Taiwanese population. Unrealistic optimism is defined as the beliefs that positive (negative) events are more (less) likely to happen to one’s self versus others. Although the bias is robust, it has been shown to be lower among people with an interdependent orientation, specifically those from a collectivist culture (e.g., Taiwan). We find that the unrealistic optimism bias is stronger (Study 1) and more resilient to change when base rates are provided (Study 2) for men as compared to women. Results are consistent with the interpretation that men have a less relationally interdependent self-construal than women. Theoretical implications for unrealistic optimism, cross-cultural psychology, as well as gender differences are discussed.
Lessons Learned and Unanswered Questions About Sexual Assault Perpetration
Authors: Abbey Antonia
Published: December 2004

The most important lesson learned about interpersonal violence in the past 20 years is the astonishingly high prevalence of sexual assault in American society. The extensiveness of unreported sexual assault has been repeatedly documented through the use of self-report data from well-constructed surveys of victims and perpetrators. In contrast, little has been learned about how to effectively reduce rates of sexual assault perpetration. Theoretically derived universal prevention programs targeted at adolescents are sorely needed.
Targets of Partner Violence
Authors: Arriaga Ximena B. , Capezza Nicole M.
Published: December 2004

Partner violence causes many negative outcomes for the target of the violence. Preventing negative outcomes in part hinges on altogether preventing the violence from occurring. There have been advances in violence prevention that the authors briefly review. However, some of the most notable advances focus on dealing with partner violence once it occurs. We now have a better understanding of different types of violence, and this has led to better interventions for perpetrators. But preventing the negative consequences of partner violence involves more than ending the violence itself; it also involves helping the targets of violence heal. The authors propose that the next decade of research on partner violence should focus on developing precise models of target coping and appropriate interventions for targets. The authors describe key variables that characterize the coping process but highlight limitations in knowledge of how these variables are related. The authors also outline several benefits of focusing on helping targets.
Top 10 Greatest “Hits”
Authors: Langhinrichsen-Rohling Jennifer
Published: December 2004

In this article, the author highlights her choice of the 10 most important recent findings from the intimate partner violence research literature, which include (a) the creation of the Conflict Tactics Scale; (b) the finding that violent acts are most often perpetrated by intimates; (c) a series of findings that indicate that women also engage in intimate partner violence; (d) the finding that intimate partner violence typically evolves out of relationship dissatisfaction; (e) the finding that there are different subtypes of domestically violent men; (f) physiological measures that have added to our knowledge of intimate partner violence; (g) the evolving intergenerational transmission of violence theory; (h) the finding that verbal abuse, neglect, and psychological abuse need to be studied alongside physical violence; (i) research on leaving abusive relationships that may inform policy about sheltering battered women; and (j) the finding that alcohol plays an important role in the production of intimate partner violence. In the conclusion, the author describes a dyadic cycle of violence that may characterize some abusive couples. She also argues for a multimodal theory that links findings obtained from individual, relationship, intergenerational, gender-specific, and cultural perspectives.
Flt3 ligand and the Flt3 receptor regulate hematopoietic cell migration by modulating the SDF-1α(CXCL12)/CXCR4 axis
Authors: Fukuda Seiji , Broxmeyer Hal E. , Pelus Louis M.
Published: December 2004

Flt3 ligand (FL) enhances hematopoietic cell proliferation and facilitates hematopoietic stem cell mobilization in vivo, while the stromal-derived factor 1α (SDF-1α, CXC ligand 12 [CXCL12])/CXC receptor 4 (CXCR4) axis is critical for their homing and trafficking. We investigated if FL and its receptor, Flt3, functionally interact with CXCL12/CXCR4 to regulate hematopoietic cell migration. FL stimulated chemokinetic activity when used alone, but synergistically enhanced short-term migration of CD34+ cells, Ba/F3 cells expressing human Flt3 (Ba/F3-Flt3), and human RS4;11 acute leukemia cells, induced by CXCL12. Moreover, overexpression of constitutively activated internal tandem duplication (ITD)–Flt3 mutants in Ba/F3 cells dramatically enhanced migration toward CXCL12. In Ba/F3-Flt3 cells, synergistic cell migration to FL plus CXCL12 was associated with enhanced phosphorylation of mitogen-activated protein kinase p42/p44 (MAPKp42/p44), cyclic adenosine monophosphate response element binding protein (CREB), and Akt, and was partially inhibited by pretreatment of cells with selective inhibitors for MAPKp42/p44, protein kinase A (PKA), or phosphatidylinositol 3–kinase (PI3-kinase), implicating these pathways in migration to FL plus CXCL12. In contrast, prolonged exposure of CD34+ or Ba/F3-Flt3 cells to FL down-regulated CXCR4 expression, inhibited CXCL12-mediated phosphorylation of MAPKp42/p44, CREB, and Akt, and impaired migration toward CXCL12. These findings suggest that FL/Flt3 may facilitate hematopoietic cell migration/homing and mobilization by enhancing or inhibiting CXCL12/CXCR4 signaling pathways and that the FL/Flt3 axis participates in trafficking of normal and transformed hematopoietic cells.
SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression
Authors: Wen Jie , Huang Suming , Rogers Heather , Dickinson Liliane A. , Kohwi-Shigematsu Terumi , Noguchi Constance Tom
Published: December 2004

Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. Here we show SATB1 family protein induction during early human adult erythroid progenitor cell differentiation concomitant with ϵ-globin expression. Erythroid differentiation of human erythroleukemia K562 cells by hemin simultaneously increases γ-globin and down-regulates SATB1 family protein and ϵ-globin gene expression. Chromatin immunoprecipitation using anti-SATB1 anti-body shows selective binding in vivo in the β-globin cluster to the hypersensitive site 2 (HS2) in the locus control region (LCR) and to the ϵ-globin promoter. SATB1 overexpression increases ϵ-globin and decreases γ-globin gene expression accompanied by histone hyperacetylation and hypomethylation in chromatin from the ϵ-globin promoter and HS2, and histone hypoacetylation and hypermethylation associated with the γ-globin promoter. In K562 cells SATB1 family protein forms a complex with CREB-binding protein (CBP) important in transcriptional activation. In cotransfection experiments, increase in ϵ-promoter activity by SATB1 was amplified by CBP and blocked by E1A, a CBP inhibitor. Our results suggest that SATB1 can up-regulate the ϵ-globin gene by interaction with specific sites in the β-globin cluster and imply that SATB1 family protein expressed in the erythroid progenitor cells may have a role in globin gene expression during early erythroid differentiation. (Blood. 2005;105:3330-3339)
Enhancing the immunostimulatory function of dendritic cells by transfection with mRNA encoding OX40 ligand
Authors: Dannull Jens , Nair Smita , Su Zhen , Boczkowski David , DeBeck Christian , Yang Benjamin , Gilboa Eli , Vieweg Johannes
Published: December 2004

The objective of this study was to investigate whether the immunostimulatory properties of human monocyte-derived dendritic cells (DCs) could be enhanced by triggering OX40/OX40L signaling. Since monocyte-derived DCs possess only low-cell surface levels of OX40L in the absence of CD40 signaling, OX40L was expressed by transfection of DCs with the corresponding mRNA. We show that OX40L mRNA transfection effectively enhanced the immunostimulatory function of DCs at multiple levels: OX40L mRNA transfection augmented allogeneic and HLA class II epitope-specific CD4+ T-cell responses, improved the stimulation of antigen-specific cytotoxic T lymphocytes (CTLs) in vitro without interfering with the prostaglandin E2 (PGE2)–mediated migratory function of the DCs, and facilitated interleukin 12 p70 (IL-12p70)–independent T helper type 1 (Th1) polarization of naive CD4+ T-helper cells. Furthermore, vaccination of tumor-bearing mice using OX40L mRNA–cotransfected DCs resulted in significant enhancement of therapeutic antitumor immunity due to in vivo priming of Th1-type T-cell responses. Our data suggest that transfection of DCs with OX40L mRNA may represent a promising strategy that could be applied in clinical immunotherapy protocols, while circumventing the current unavailability of reagents facilitating OX40 ligation.
Über die Reaktion von Benzhydroxamsäureestern mit Diazomethan
Authors: Blaser R. , Imfeld P. , Schindler O.
Published: December 2004

Benzhydroxamsäure und im Phenylkern substituierte Analoge bilden mit α‐Halogencarbonsäureestern Benzhydroxamsäureester (IV in Tab.1). Diese reagierten mit Diazomethan stereospezifisch zu den entsprechenden syn‐Methyl‐benzhydroximsäureestern (V in Tab.1.). Die Zuordnung der Stereochemie basiert auf dem Aufbau von XIV und XVIII aus den beiden 3‐O‐Methyl‐benzhydroxamsäuren XII und XIII, deren Stereochemie gesichert ist.
Stoffwechselprodukte von Mikroorganismen. 75. Mitteilung [1]. Synthese des Ferrichroms; 2. Teil
Authors: Keller‐Schierlein W. , Maurer B.
Published: December 2004

Ferrichrome, a biologically active sideramine isolated from cultures of several strains of fungi, was synthesized starting from δ‐nitro‐L‐norvaline and glycine. The intermediate trinitro‐cyclohexapeptide 17 could be obtained in high yield by SCHWYZER's method from the corresponding open‐chain hexapeptide 16.
Konstitution von Palustridin
Authors: Green C. L. , Mayer C. , Eugster C. H.
Published: December 2004

Palustridine (I, C18H31N3O3), which co‐occurs with palustrine in Equisetum palustre L., has been shown to be Nb‐formyl‐palustrine. Hydrolysis with dilute mineral acid yields palustrine, and formylation of the latter gives palustridine. The mass spectral fragmentation pattern differs from that of palustrine, and is very similar to that of Nb‐acetylpalustrine. The earlier proposed skeleton of palustrine is independently confirmed.
Zur Kenntnis der VAN SLYKE‐Reaktion des Muscimols und anderer 3‐Hydroxyisoxazole. 32. Mitteilung über Inhaltsstoffe von Fliegenpilzen
Authors: Fràter‐Schröder M. , Good R. , Eugster C. H.
Published: December 2004

3‐Hydroxyisoxazole werden unter sehr milden Bedingungen zu instabilen N‐Nitrosoverbindungen nitrosiert, welche in verdünnter Essigsäure rasch in N2O und CO2 zerfallen. Die Reaktion kann als Mikromethode zur Erkennung von 3‐Hydroxyisoxazolen benutzt werden.

Die Synthese mehrerer neuer 3‐Hydroxyisoxazole wird angegeben.
Protonenresonanzspektren von Pteridinen (VI). Mono‐ und Dikationen von 2‐Amino‐4‐oxo‐3, 4‐dihydropteridinen
Authors: Dieffenbacher A. , Philipsborn W.
Published: December 2004

Proton NMR. spectra of 18 pteridines have been measured in strongly acidic solutions. In trifluoroacidic acid mono‐cations are formed whereas in fluorosulfonic acid double protonation occurs. For the first time di‐cations of pteridines are described, and the structures of these species are determined by NMR. and UV. data. The chemical shifts of the NH2 protons in the mono‐cations and of the methyl protons in the mono‐ and di‐cations follow linear correlations with the basic pKa values. From NMR. variable temperature measurements the energy barrier to internal rotation in the amidinium system has been ddtermined for both cations. The results are discussed with particular regard to the structure of the mono‐and di‐cations.
Zur Deutung des UV.‐Spektrums von Pyridin‐N‐oxid
Authors: Seibold K. , Wagnière G. , Labhart H.
Published: December 2004

From measurements of the influence of an electric field on the absorption spectrum of pyridine‐N‐oxide it is concluded that the 330 nm band is polarized perpendicular to the dipole moment, while the 280 nm transition moment lies parallel. Furthermore from these experiments the dipole moments in both excited states have been determined (Table 1). PARISER‐PARR‐POPLE‐calculations as well as CNDO‐calculations admit an assignment of the 330 nm band to anA1→B1, π → π* transition and of the 280 nm band to anA1→A1, π → π* transition. Thereby energy, polarization, intensity of the transition, and the dipole moments of the excited states have been taken into consideration. This assignment does not exclude the possibility of a weakn‐π* transition at approximately the same wavelength as theA1→B1transition.
Lösungsmitteleffekte in Kernresonanzspektren gesättigter Kohlenwasserstoffe (III). Unterscheidung unpolarer und polarer Effekte bei Steroiden
Authors: Winkler T. , von Philipsborn W.
Published: December 2004

Benzene‐induced proton NMR. solvent shifts of methyl and methylene groups in 25 acyclic and cyclic saturated hydrocarbons have been studied. The dependence of magnitude and sign of these unpolar effects upon the molecular shape is again demonstrated. Solvent shifts in polar solutes (hydroxy‐ and keto‐steroids) are shown to originate from a superposition of polar and unpolar effects. The implications for the interpretation of small solvent shifts in polar solutes are discussed.
Tetrafluordiazabuten‐Derivate aus Chlorcyan
Authors: Alt K. O. , Weis C. D.
Published: December 2004

Cyanogenchloride reacts in liquid hydrogenfluoride with fluorides of some aliphatic hydrocarbons to yield derivatives of 2,4,4,4‐tetrafluoro‐1,3‐diazabut‐2‐ene. The mechanism of its formation is explained in terms of an intermediate fluorinated linear dimerization product of cyanogenchloride. Reactions of the N‐trifluoromethylgroup are reported.
Utilisation d'ylides du phosphore non stabilisés en chimie des sucres. II. Action du méthylthiométhylène‐triphénylphosphorane sur les aldéhydo‐surces
Authors: Tronchet J. M. J. , Jaccard‐Thorndahl Mme S. , Baehler Br.
Published: December 2004

The action of methylthiomethylene‐triphenylphosphorane on 2,3: 4,5‐di‐O‐isopropylidene‐Aldehydo‐‐L‐arabinose led with good yield to the corresponding unsaturated sugar which underwent electrophilic addition with a high regiospecificity. This provides a useful new route for a one‐carbon chain extension in the carbohydrate series.