bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional morphology and gene expression in the Drosophilablastoderm at cellular resolution I: data acquisition pipeline
Authors: Luengo Hendriks Cris L , Keränen Soile VE , Fowlkes Charless C , Simirenko Lisa , Weber Gunther H , DePace Angela H , Henriquez Clara , Kaszuba David W , Hamann Bernd , Eisen Michael B , Malik Jitendra , Sudar Damir , Biggin Mark D , Knowles David W
Published: December 2006

Background

To model and thoroughly understand animal transcription networks, it is essential to derive accurate spatial and temporal descriptions of developing gene expression patterns with cellular resolution.

Results

Here we describe a suite of methods that provide the first quantitative three-dimensional description of gene expression and morphology at cellular resolution in whole embryos. A database containing information derived from 1,282 embryos is released that describes the mRNA expression of 22 genes at multiple time points in the Drosophila blastoderm. We demonstrate that our methods are sufficiently accurate to detect previously undescribed features of morphology and gene expression. The cellular blastoderm is shown to have an intricate morphology of nuclear density patterns and apical/basal displacements that correlate with later well-known morphological features. Pair rule gene expression stripes, generally considered to specify patterning only along the anterior/posterior body axis, are shown to have complex changes in stripe location, stripe curvature, and expression level along the dorsal/ventral axis. Pair rule genes are also found to not always maintain the same register to each other.

Conclusion

The application of these quantitative methods to other developmental systems will likely reveal many other previously unknown features and provide a more rigorous understanding of developmental regulatory networks.
Evolutionary conservation of domain-domain interactions
Authors: Itzhaki Zohar , Akiva Eyal , Altuvia Yael , Margalit Hanah
Published: December 2006

Background

Recently, there has been much interest in relating domain-domain interactions (DDIs) to protein-protein interactions (PPIs) and vice versa, in an attempt to understand the molecular basis of PPIs.

Results

Here we map structurally derived DDIs onto the cellular PPI networks of different organisms and demonstrate that there is a catalog of domain pairs that is used to mediate various interactions in the cell. We show that these DDIs occur frequently in protein complexes and that homotypic interactions (of a domain with itself) are abundant. A comparison of the repertoires of DDIs in the networks of Escherichia coli, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens shows that many DDIs are evolutionarily conserved.

Conclusion

Our results indicate that different organisms use the same 'building blocks' for PPIs, suggesting that the functionality of many domain pairs in mediating protein interactions is maintained in evolution.
Myosin Va Mutation in Rats Is an Animal Model for the Human Hereditary Neurological Disease, Griscelli Syndrome Type 1
Authors: TAKAGISHI YOSHIKO , MURATA YOSHIHARU
Published: December 2006

Abstract:  A spontaneous neurological mutation, dilute‐opisthotonus (dop), was discovered in our breeding colony of Wistar rats. We found that the mutation affected the gene encoding Myosin Va (MyoVA), an actin‐based molecular motor. Analysis of the myosin Va (Myo5a) gene of the dop genome showed the presence of a complex rearrangement consisting of a 306‐bp inversion associated with 217‐bp and 17‐bp deletions. A 141‐bp exon is skipped in the dop transcript, producing a dop cDNA with a 141 in‐frame deletion in the sequences encoding the head region. Expression of the MyoVA protein is severely impaired in the brains of dop homozygous rats, suggesting they have a null mutation for Myo5a. In a morphological analysis of the cerebella of dop rats, we found an absence of smooth endoplasmic reticulum (SER) and of inositol 1,4,5‐triphosphate (IP3) receptors in the dendritic spines of Purkinje cells (PC). The SER acts as an intracellular Ca2+ store and IP3‐mediated Ca2+ signaling in dendritic spines plays a critical role in synaptic regulation. We therefore measured synaptic transmission and long‐term depression (LTD), a form of synaptic plasticity underlying cerebellar motor learning, at PC synapses in the cerebella of dop rats. We found that synaptic transmission at the PC synapses is largely normal, whereas the LTD is deficient due to a decrease in IP3‐mediated Ca2+ release from the SER in the PC spines of the dop cerebella. These findings may account for the ataxic movements and clonic convulsions displayed by dop rats. They also contribute to our understanding of the neurological disease mechanisms of the human hereditary disease Griscelli syndrome type 1, which is caused by mutation of the Myo5a gene.
Cytoplasmic Lipid Droplets
Authors: FUJIMOTO TOYOSHI , OHSAKI YUKI
Published: December 2006

Abstract:  Cytoplasmic lipid droplets (LDs) exist in virtually any kind of cell. They have a core of lipid esters covered by the surface phospholipid monolayer. A number of proteins related to various cell functions are present in LDs and/or LD‐rich subcellular fractions, suggesting that LDs are an independent organelle that is engaged in various cellular activities. Furthermore, a recent study suggested that LDs are a platform where the proteasomal and autophagic pathways converge. The molecular composition and architecture of LDs are discussed here, with special reference to the technical difficulties encountered when analyzing this unique organelle.
Alleviating Neurodegeneration by an Anticancer Agent
Authors: WAZA MASAHIRO , ADACHI HIROAKI , KATSUNO MASAHISA , MINAMIYAMA MAKOTO , TANAKA FUMIAKI , SOBUE GEN
Published: December 2006

Abstract:  Heat shock proteins (HSPs) that function mainly as molecular chaperones play an important role in the folding and quality control of proteins. Compared with these chaperones, Hsp90 is unique in that it binds to substrate proteins, called Hsp90 client proteins. Hsp90 is involved in the folding, activation, and assembly of its client proteins in association with its co‐chaperones. Because numerous oncoproteins belonging to the Hsp90 client protein family are selectively degraded by Hsp90 inhibitors, 17‐allylamino‐17‐demethoxygeldanamycin (17‐AAG), a first‐in‐class Hsp90 inhibitor, is now under clinical trials as a novel molecular‐targeted agent for a wide range of malignancies. In spinal and bulbar muscular atrophy (SBMA), the pathogenic gene product is polyglutamine (polyQ)‐expanded androgen receptor (AR), which belongs to the Hsp90 client protein family and is known to be degraded by 17‐AAG. We have recently demonstrated that administration of an anticancer agent 17‐AAG significantly ameliorated polyQ‐mediated motor neuron degeneration by reducing the total amount of mutant AR. The ability of 17‐AAG to degrade mutant protein would be directly applicable to SBMA and other neurodegenerative diseases in which the disease‐causing proteins also belong to the Hsp90 client protein family. Our proposed therapeutic approach using a novel anticancer agent 17‐AAG has emerged as a candidate for molecular‐targeted therapies for neurodegenerative diseases.
Role of Polyunsaturated Fatty Acids for Misfolding Protein Aggregations
Authors: KIM YEON‐JEONG , TAKAHASHI RYOSUKE
Published: December 2006

Abstract:  Numerous neurodegenerative diseases are accompanied by highly insoluble inclusions of protein aggregates within characteristic neuronal populations. Recent in vitro studies have advanced new aspects of protein aggregates and their cytotoxicity. Aggregations of unfolded proteins escape the cellular quality‐control system, such as chaperone and proteasome, which is a common feature of aggregates‐associated neurodegeneration. Based on this idea, several factors may provide protein aggregates‐favoring conditions that are closely involved in progression of diseases. In particular, we focused on polyunsaturated fatty acids as an important modulator for unfolded protein‐aggregation in relation to disease pathogenesis.
Aortic Aneurysms as a Source of Circulating Interleukin‐6
Authors: DAWSON JOE , COCKERILL GILLIAN , CHOKE EDWARD , LOFTUS IAN , THOMPSON MATT M.
Published: December 2006

Abstract:  In keeping with the inflammatory paradigm of abdominal aortic aneurysm (AAA) pathophysiology, in vitro studies suggest that aneurysms secrete the proinflammatory cytokine interleukin‐6 (IL‐6). Circulating IL‐6 levels are higher in patients with AAA with elevated circulating IL‐6 an independent risk factor for cardiovascular mortality. To investigate whether aneurysms secrete IL‐6 into the circulation, arterial IL‐6 was measured from within the aorta in three groups of patients undergoing endovascular procedures; 27 AAA, 10 thoracic aneurysms (TA), and 15 controls. Overall, IL‐6 was higher in the aneurysm groups (P < 0.0008) with significant rises corresponding to positions downstream to the aneurysm in both AAA and TA. There were no significant differences in IL‐6 with aortic position in the control group. These data support the hypothesis that aneurysms secrete IL‐6 into the circulation and may account for the high cardiovascular mortality observed in patients with aneurysms.
Pathogenesis of Thoracic and Abdominal Aortic Aneurysms
Authors: GUO DONG‐CHUAN , PAPKE CHRISTINA L. , HE RUMIN , MILEWICZ DIANNA M.
Published: December 2006

Abstract:  The major disease processes affecting the aorta are aortic aneurysms and dissections. Aneurysms are usually described in terms of their anatomic location, with thoracic aortic aneurysms (TAAs) involving the ascending and descending aorta in the thoracic cavity and abdominal aortic aneurysms (AAAs) involving the infrarenal abdominal aorta. Both thoracic and abdominal aortas are elastic arteries, and share similarities in their physical structures and cellular components. However, thoracic and abdominal aortas differ in their biochemical properties and the origin of their vascular smooth muscle cells (VSMCs). These similarities and differences between thoracic and abdominal aortas provide the basis for the various pathologic mechanisms observed in this disease. This review focuses on the comparison of the pathologic mechanisms involved in TAA and AAA.
Attenuation of Experimental Aortic Aneurysm Formation in P‐Selectin Knockout Mice
Authors: HANNAWA KEVIN K. , CHO BRENDA S. , SINHA INDRANIL , ROELOFS KAREN J. , MYERS DANIEL D. , WAKEFIELD THOMAS J. , STANLEY JAMES C. , HENKE PETER K. , UPCHURCH GILBERT R.
Published: December 2006

Abstract:  The aim of this study was to determine the role of P‐selectin, an adhesion molecule found on the surface of activated platelets and endothelial cells during experimental aortic aneurysm formation. Infrarenal abdominal aortas of C57 black wild‐type (WT) mice and P‐selectin knockout (PKO) mice were measured in situ and then perfused with porcine pancreatic elastase (0.332 U/mL). Whole blood was drawn from the tail artery on day 2 pre‐perfusion to determine total and differential white blood cell (WBC) counts. On day 14 postperfusion, aortic diameters (AD) of WT mice (N= 19) and PKO mice (N= 9) were measured. An aortic aneurysm was defined as a 100% or greater increase in AD from pre‐perfusion measurement. Immunohistochemistry, including H&E, trichrome and von Gieson staining, was performed on harvested aortic tissue. Statistical analysis was performed by t‐test and Fisher's exact test. There were no significant differences in peripheral leukocyte counts at baseline between the two groups. WT mice had significantly larger AD compared to PKO mice at day 14 postperfusion (116 % vs. 38 %, P < 0.001). Aortic aneurysm penetrance was 52% in WT mice, while 0% (P= 0.01) of PKO mice formed aneurysms. On histologic examination, WT mouse aortas were associated with a significant inflammatory response and degradation of elastin and collagen fibers, while PKO mouse aortas lacked signs of inflammation or vessel wall injury. P‐selectin deficiency attenuates aneurysm formation in the elastase aortic perfusion model. This was associated with a blunting of the inflammatory response and preserved vessel wall intergrity following elastase perfusion in the P‐selectin knockout mice. Further investigation to elucidate the independent contributions of endothelial cell and platelet P‐selectin in experimental aortic aneurysm formation is required.
The Candidate Gene Approach to Susceptibility for Abdominal Aortic Aneurysm
Authors: TILSON M. DAVID , RO CHARLES Y.
Published: December 2006

Abstract:  There are two approaches to gene discovery for diseases when genetic susceptibility has been implicated by clinical genetic or case‐control studies: (1) genome‐wide screening and (2) evaluation of candidate genes. Each has specific advantages and disadvantages. The principal advantage of genome‐wide screening is that it is impeccably objective in as much as it proceeds without any presuppositions regarding the importance of specific pathobiological features of the disease process. The principal disadvantage is that such a study is expensive and resource intensive. A large population of enrolled patients and multidisciplinary teams of investigators cooperating from several institutions are usually required. The alternative approach of evaluating candidate genes can be pursued by a small independent laboratory with limited funding and resources, a small collection of clinical specimens, and a small number of team players. The disadvantage is that it is by necessity highly subjective in the process of selecting specific candidates among many reasonable possibilities. There is no a priori assurance that effort will not be expended on one or more candidates that turn out in the end to be failures. This report reviews efforts in our laboratory to evaluate four genes as candidates. One of these tissue inhibitor of metalloprotease 1(TIMP1) led to the description of a polymorphism, but not a conclusive mutation. The other three (HLA‐DR‐15, ferritin light chain (FTL), and collagen XI‐alpha‐1 (COL11A1) are subjects of continuing interest.
Aneurysm Outreach Inc., a Nonprofit Organization, Offers Community‐Based, Ultrasonography Screening for Abdominal Aortic Aneurysms
Authors: ARRINGTON SHEILA , OGATA TORU , DAVIS P. MICHAEL , SAM ALBERT D. , HOLLIER LARRY H. , TROMP GERARD , KUIVANIEMI HELENA
Published: December 2006

Abstract:  Aneurysm Outreach Inc. (AOI;

http://www.alink.org

) is a nonprofit volunteer organization founded in 1999 whose aim is to (a) raise public awareness about aneurysms; (b) stimulate and fund genetic research through donations; and (c) coordinate a support network for aneurysm patients and their families. Since abdominal ultrasonography examination of an asymptomatic individual is not presently reimbursed by health insurance in the United States, one of the initiatives supported by AOI is to have free ultrasonography screening for abdominal aortic aneurysm (AAA) for those most at risk. One of the initiatives supported by AOI is to have free ultrasonography screening for abdominal aortic aneurysm (AAA). To meet this goal, a free screening program was initiated in September 2001 and by November 2004 approximately 3,000 participants were screened and 61 (2.0%) participants were confirmed to have a dilated aorta and were referred to their primary care physicians or vascular surgeons for further follow‐up and treatment, if indicated.
Combining Open and Endovascular Approaches to Complex Aneurysms
Authors: LEMAIRE SCOTT A.
Published: December 2006

Abstract:  Patients with aortic aneurysms commonly present with anatomic issues that preclude them from receiving purely endovascular repairs. In these situations, open surgical procedures can be used to manage anatomic problems and facilitate endovascular aneurysm repair. This report focuses on combined approaches that enable repair of abdominal or thoracoabdominal aortic aneurysms that involve the mesenteric and/or renal circulation. Current experience with combined open/endovascular repairs is essentially anecdotal. The common feature among the open procedures is establishment of extra‐anatomic perfusion of the visceral arteries to enable ligation and subsequent coverage of their ostia during endograft placement. The existing reports are notable for the marked variability in many factors including extent of aneurysm repair, surgical approach, mode of visceral revascularization, conduit for bypass, and type of endovascular device used. Overall, current reports demonstrate that patients with limited physiologic reserve and complex aortic anatomy can be treated successfully by combining open and endovascular repairs. As endograft design and endovascular techniques continue to improve, combined approaches are likely to play an increasingly important role in the treatment of extensive aortic disease.
The Intraluminal Thrombus as a Source of Proteolytic Activity
Authors: SWEDENBORG JESPER , ERIKSSON PER
Published: December 2006

Abstract: Most abdominal aortic aneurysms (AAAs) with a diameter indicating need for surgical repair contain intraluminal thrombus (ILT). The development of AAA is linked to degradation of elastin and collagen. These changes are more pronounced in the aneurysm wall covered by the ILT, which also shows more signs of inflammation and is thinner compared to the aneurysm wall exposed to flowing blood. The rate of increase in diameter of AAA correlates with increased thrombus growth and rupture. CT examinations of patients with rupture have demonstrated contrast appearing in the thrombus suggesting bleeding into it. Studies using gene array of human aneurysm specimens have shown that most matrix metalloproteinases (MMP) were upregulated in the thrombus‐free wall. Analyses by zymography, however, demonstrate gelatinase activity in the interface between the thrombus and the underlying wall and in the media of the wall not covered by a thrombus. The thrombus contains large amounts of neutrophils. Neutrophil gelatinase associated lipocalin (NGAL) is involved in the regulation of MMP‐9 activity and prevents its inactivation, thus augmenting the proteolytic effect. It has been identified in all layers of the ILT. The presence of NGAL/MMP‐9 complexes throughout the thrombus and in the thrombus‐covered wall may contribute to the increased proteolytic degradation seen in this wall segment. In conclusion, the presence, growth, and thickness of the ILT have been shown to be associated with growth and risk of rupture. The wall underlying the thrombus is thinner and shows more signs of proteolytic degradation. Increased proteolytic activity by MMP‐9 may be mediated by binding to NGAL.
Stage-Specific Expression of Androgen Receptor, Follicle-Stimulating Hormone Receptor, and Anti-Müllerian Hormone Type II Receptor in Single, Isolated, Human Preantral Follicles: Relevance to Polycystic Ovaries
Authors: Rice Suman , Ojha Kamal , Whitehead Saffron , Mason Helen
Published: December 2006

Context: Recent evidence indicates that the increase in follicle numbers seen in polycystic ovary syndrome occurs early in folliculogenesis, with androgens being a likely causative candidate. In primates and sheep, androgen excess in utero results in ovarian changes similar to those in polycystic ovary syndrome. There is also increasing interest in the role of anti-Müllerian hormone (AMH) in early folliculogenesis because AMH knockout mice have an early depletion of their stock of primordial follicles. Initiation and early folliculogenesis may therefore be under negative control by AMH and positive control by androgens.

Objective: Because AMH signals exclusively through its type II receptor (AMHRII), the aim of this study was to determine and colocalize the stage-specific expression of AMHRII, androgen receptor (AR), and FSH receptor (FSHR) mRNA in individual, well-characterized preantral follicles.

Method: Follicles were isolated from human ovarian cortex obtained from either oophorectomies or cortical biopsies at cesarean section. Expression of AR, FSHR, and AMHRII mRNA was determined using a nested RT-PCR protocol.

Results: AR mRNA was not detected in any primordial follicles but was from the transitional stage onward. The number of AR-positive follicles increased at each progressive growth stage. The expression of AR preceded that of FSHR, and only a small percentage of primary follicles expressed FSHR. AMHRII expression was rarely detected.

Conclusions: This is the first study to identify the expression of AR in human transitional follicles. Results suggest a role for androgens in promoting early follicle growth and challenging the hypothesis that AMH exerts a direct, inhibitory effect on follicles at this stage.
Ageing, gender and cardiac sarcolemmal KATP channels
Authors: Jovanović Aleksandar
Published: December 2006

Sarcolemmal ATP-sensitive K+ (KATP) channels are abundant in cardiac myocytes where they couple the cellular metabolic state with membrane excitability. Structurally, these channels are composed of Kir6.2, a pore-forming subunit, SUR2A, a regulatory subunit, and at least four accessory proteins. The activation of KATP channels occurs during ischaemia to promote cardiac viability under this adverse condition. Age-dependent changes in the myocardial susceptibility to ischaemia have been reported in experimental animals as well as in humans. Recent research has demonstrated that ageing is associated with a decrease in the number of cardiac sarcolemmal KATP channels in hearts from females, but not males. This alteration is likely to be due to an age-dependent decrease in the concentration of circulating estrogens. In the heart, SUR2A is the least expressed protein of all KATP channel-forming proteins. The consequence of this phenomenon is that the level of SUR2A is the main factor controlling the number of sarcolemmal KATP channels. Estrogens specifically up-regulate SUR2A and govern the number of sarcolemmal KATP channels, and this may explain the effect of decreasing estrogen levels on the heart. An age-dependent decrease in the number of sarcolemmal KATP channels generates a cardiac phenotype more sensitive to ischaemia, which seems to be responsible for the ageing-associated decrease in myocardial tolerance to stress that occurs in elderly women.
Effects of the Chinese prescription Kangen-karyu and its crude drug Tanjin on ageing process in rats
Authors: Yokozawa Takako , Cho Eun Ju , Okamoto Takuya , Sei Yasuo
Published: December 2006

The effects of the Chinese prescription Kangen-karyu and its crude drug Tanjin on the ageing process were investigated in rats. Diets supplemented with Kangen-karyu and Tanjin extracts decreased glycosylated protein levels in serum, a risk marker of ageing and ageing-related diseases. In addition, they inhibited the levels of thiobarbituric acid reactive substance in the serum and liver; Kangen-karyu in particular led to a strong decrease in hepatic mitochondrial thiobarbituric acid reactive substance. The decline in the reduced glutathione/oxidized glutathione ratio in the liver observed with ageing was ameliorated by Kangen-karyu and Tanjin, while these groups attenuated the increase in glutathione peroxidase activity of hepatic tissue against ageing. This suggests that Kangen-karyu and Tanjin regulate the glutathione redox cycle that maintains the cellular redox condition against age-related oxidative stress. Moreover, the overexpression of cytoplasmic cytochrome c observed with ageing was attenuated by Kangen-karyu and Tanjin. This provides new evidence that Kangen-karyu and Tanjin inhibit leakage of superoxide in mitochondria and attenuate cellular oxidative damage. Furthermore, Kangen-karyu and Tanjin would maintain mitochondrial function with ageing through the regulation of related protein expression such as bax and bcl-2 proteins. In addition, Kangen-karyu reduced the expression of nuclear factor kappa B; Kangen-karyu and Tanjin did not affect the expression of inhibitor kappa B. The present study demonstrated that Kangenkaryu prevented oxidative damage and mitochondrial dysfunction with ageing. Furthermore, Kangen-karyu showed a stronger protective effect against ageing by oxidative stress than Tanjin, probably through synergistic and/or additive effects.
The impact of adenosine and A2B receptors on glucose homoeostasis
Authors: Rüsing D , Müller C E , Verspohl E J
Published: December 2006

Adenosine and adenosine receptor antagonists are involved in glucose homoeostasis. The participating receptors are not known, mainly due to a lack of specific agonists and antagonists, but are reasonable targets for anti-diabetic therapy. The stable, albeit nonselective, adenosine analogue NECA (5′-N-ethylcarboxamidoadenosine) (10 μM) reduced glucose-stimulated insulin release from INS-1 cells. This was mimicked by A1-(CHA), A2A-(CGS-21680) and A3-receptor agonists (Cl-IB-MECA). Two newly synthesized A2B-receptor antagonists, PSB-53 and PSB-1115, counteracted the inhibitory effect of NECA. These in-vitro effects were mirrored by in-vivo data with respect to CHA, CGS and Cl-IB-MECA. Distinct concentrations of either PSB-53 or PSB-1115 reversed the decrease in plasma insulin induced by NECA. This was not mimicked by a corresponding change in blood glucose. The effect of PSB-1115 was also obvious in diabetic GotoKakizaki rats: plasma insulin was increased whereas blood glucose was unchanged. During most experiments the effects on blood glucose were not impressive probably because of the physiologically necessary homoeostasis. The adenosine levels were not different in normal Wistar rats and in diabetic GotoKakzaki rats. Altogether the A2B-receptor antagonists showed an anti-diabetic potential mainly by increasing plasma insulin levels under conditions when the adenosine tonus was elevated in-vivo and increased insulin release in-vitro.
Alteration of vascular reactivity in diabetic human mammary artery and the effects of thiazolidinediones
Authors: Irat Ali Murat , Aslamaci Sait , Karasu Cimen , Ari Nuray
Published: December 2006

Vascular reactivity was investigated in endothelium-denuded human internal mammary artery (IMA) rings from type 2 diabetic patients. It was also investigated whether insulin sensitizer thiazolidinedione drugs, pioglitazone and rosiglitazone, can directly affect the reactivity of IMA. Using organ bath techniques, cumulative concentration-response curves to phenylephrine (PE), KCl, cromakalim (CRO) and sodium nitroprusside (SNP) were constructed in diabetic and non-diabetic IMA rings. Means of maximal responses (% Emax) and pEC50 values (sensitivity) were compared. Emax values and the sensitivity to PE and KCl were increased while KATP-channel-mediated relaxations were reduced significantly in diabetic rings compared with non-diabetic rings (n = 5–12, P < 0.05). No changes were observed for SNP responses (n = 5, P > 0.05). Incubations with pioglitazone (1 and 10 μM) and rosiglitazone (1 and 20 μM), for 30 min, did not affect KATP-channel-mediated relaxations (n = 5 each, P > 0.05). Pioglitazone partly inhibited pre-contractions of PE and KCl at 10 μM, rosiglitazone did not. Vascular dysfunction observed in diabetic IMA may be of specific importance since they are widely used as coronary bypass material. Thiazolidinedione drugs may not worsen arterial dilatation through KATP channels in ischaemic or hypoxic insults in diabetic patients who are prone to such conditions. Pioglitazone has vasorelaxant property in the grafts.
Anti-inflammatory activity of the synthetic C-C biflavonoids
Authors: Park Haeil , Kim Young Hoon , Chang Hyeun Wook , Kim Hyun Pyo
Published: December 2006

To find anti-inflammatory agents based on plant constituents, the effects of six synthetic C-C biflavonoids connecting with different positions of C-C bond between flavone monomers (a: 4′-4′, b: 4′-3′, c: 4′-6, d: 3′-6, e: 6-6, f: 4′-3) were examined on PGE2 and nitric oxide (NO) production from lipopolysaccharide (LPS)-treated macrophages, RAW 264.7. Among the compounds tested, the biflavonoids d, e, and f showed a considerable inhibition of cyclooxygenase-2 (COX-2)-mediated PGE2 production at concentrations up to 50 μM, while the derivative c exerted cytotoxic effects on RAW cells. Especially, the biflavonoid e possessed the most potent inhibitory activity of PGE2 production with an IC50 of 3.7 μM, compared with an IC50 of 8.2–20.7 μM by ginkgetin (natural biflavonoid). Western blot and reverse transcriptase-polymerase chain reaction analyses have shown that the inhibition of PGE2 production by these synthetic derivatives was mediated at least in part by COX-2 inhibition, but not by COX-2 down-regulation. Meanwhile, these synthetic biflavonoids did not considerably inhibit inducible nitric oxide synthase-mediated NO production at concentrations up to 50 μM. When intraperitoneally administered, the biflavonoid e showed a significant anti-inflammatory activity (22.2% inhibition) against rat carrageenan-induced paw oedema at 5 mg kg−1. The biflavonoid e may be used as a synthetic lead for developing new anti-inflammatory agents.
Expression and function of α-smooth muscle actin during embryonic-stem-cell-derived cardiomyocyte differentiation
Authors: Clément Sophie , Stouffs Michael , Bettiol Esther , Kampf Sandy , Krause Karl-Heinz , Chaponnier Christine , Jaconi Marisa
Published: December 2006

Three α-muscle actin isoforms are sequentially expressed during in vivo cardiac development. α-Smooth muscle actin is first and transiently expressed, followed by α-skeletal and finally α-cardiac actin. The significance of these transitions in actin gene expression during myogenesis remains to be determined. To understand whether actin isoforms have specific functions during cardiac development and cardiomyocyte contractility, we have hampered α-smooth muscle and α-skeletal actin expression and organization during embryonic stem cell differentiation towards cardiomyocyte. We show that the sequence of actin isoform expression displays similar pattern in the in vitro model and in mouse heart embryogenesis. Treatment with an interfering fusion peptide containing the N-terminal sequence of α-smooth muscle actin during a time window preceding spontaneous beating, prevents proper cardiac sarcomyogenesis, whereas α-skeletal actin-fusion peptide has no effect. Knockdown of α-smooth muscle actin in embryonic stem cells using RNA interference also affects cardiac differentiation. The application of both fusion peptides on beating embryoid bodies impairs frequency. These results suggest specific functional activities for actin isoforms in cardiogenesis and cardiomyocyte contractility.
Self-assembly of Birnessite Manganese Dioxide into Monodisperse Honeycomb and Hollow Nanospheres
Authors: Chen Hongmin , He Junhui
Published: December 2006

Monodisperse honeycomb and hollow nanospheres of ordered birnessite manganese dioxide nanoplatelets were facilely synthesized in high yields via the redox reaction of KMnO4 and oleic acid and following self-assembly of produced nanoplatelets.
Application of a Water Soluble Alkoxysilane for the Formation of Mesoporous Silica from Nonionic Surfactant Micelles Bearing Cholesterol
Authors: Takahashi Shun , Ikkai Yasunari , Rodriguez-Abreu Carlos , Aramaki Kenji , Ohsuna Tetsu , Sakamoto Kazutami
Published: December 2006

A water soluble silica precursor, tetrahydroxyethyl orthosilicate (THEOS), was used for the synthesis of mesoporous silica from micellar solutions of a nonionic surfactant bearing cholesterol moiety (ChEO10), which also forms a variety of lyotropic liquid crystal (LLC) structures. The resulting mesoporous silica showed ribbon-like structures, both in μm and nm scale, corresponding to the rectangular LLC phase of ChEO10. We propose the use of THEOS as a novel silica precursor for the investigation of tailored imprinting of LLC topology into the mesoporous silica.
Helix-dimer–Random-coil Thermal Switching Process of Ethynylhelicene Heptamer Highly Sensitive to Its Environment
Authors: Sugiura Hiroki , Yamaguchi Masahiko
Published: December 2006

An acyclic ethynylhelicene heptamer reversibly switches its structure in solution between a helix dimer at low temperatures and random coils at high temperatures. The structural change can be repeated by alternating heating and cooling. The process monitored by CD exhibited various patterns of Δε/time profiles depending on changes in temperature, concentration, and solvent type. This single compound provides diverse outputs upon thermal input.
Psoriasis Following Growth Hormone Therapy in a Child
Authors: Pirgon Ozgur , Atabek Mehmet Emre , Sert Ahmet
Published: December 2006

Objective:

To report a case of psoriasis that developed following growth hormone treatment.

Case Summary:

An 8-year-old boy was admitted to our pediatric endocrinology department because of short stature (<3rd percentile). A dopamine stimulation test and an insulin tolerance test revealed growth hormone (GH) deficiency with a normal cortisol response. His insulin-like growth factor 1 (IGF-1) level (9 ng/mL; reference range 113–261) was under the limits for his age and sex. Six months after the initiation of treatment with recombinant human GH 0.33 mg/kg/wk, the patient presented with a 10 day history of desquamation and a burning sensation in his right knee and hip. Lesions of erythematous papules consistent with plaques of psoriasis were present. Histologic findings from skin biopsies were consistent with psoriasis. The GH dose was reduced to 0.2 mg/kg/wk and treatment for psoriasis (including hydrocortisone and clemastine) was started. Three months after those interventions, the plaques had resolved.

Discussion:

Previous studies proposed that the extent and severity of psoriasis correlate with GH levels, although psoriatic patients, in general, have normal GH and IGF-1 levels. The Naranjo probability scale indicated that the development of psoriasis was probably associated with GH therapy.

Conclusions:

This case suggests that the development of psoriasiform lesions in a previously unaffected individual represents an adverse effect of GH treatment, occurring at higher doses, with higher IGF-1 levels.
Everyday Talk: Its Role in Assessment and Treatment for Individuals With Aphasia
Authors: Armstrong Elizabeth , Mortensen Lynne
Published: December 2006

This article discusses the significance of conversation in current clinical practice with individuals with aphasia and their conversation partners. It explores the nature of everyday talk, and provides an overview of how studies to date have examined the conversations of individuals with aphasia and have provided some promising treatment avenues. It also proposes another framework, Speech Function Analysis, that may assist further in incorporating conversational principles into the therapy context. The framework provides a system network for examining speech functions in dialogue, while considering the effects of both lexical and syntactic limitations, and context. Examples of conversations between three individuals with aphasia and their partners are used to illustrate the analysis. The authors suggest that further knowledge of both aphasic speakers' and their partners' interactions as well as clinician–client interactions may increase our insights into this area, and make authentic and meaningful conversation more accessible in the clinical situation and beyond.
Terminology and Methodology in the Assessment of Cognitive-Linguistic Disorders
Authors: Body Richard , Perkins Michael R.
Published: December 2006

The term ‘cognitive-linguistic’ has been widely adopted in descriptions of a variety of communication disorders of neurogenic origin. Despite this, clear agreement on the meaning of the term has yet to be reached, with the result that it is used both inconsistently and misleadingly. This lack of terminological clarity also undermines the assessment of complex communicative function. In this article the terminology associated with complex communication disorders is discussed and a simple framework for conceptualising cognitive-linguistic function is outlined. On the basis of this it is proposed that some currently available assessments that purport to measure cognitive-linguistic skills in fact have less explanatory power than other assessments that are often not specifically targeted at communication. Further, it is suggested that the framework offers an ecologically valid basis for the systematic assessment of cognitive-linguistic function.
Ca2+from One or Two Channels Controls Fusion of a Single Vesicle at the Frog Neuromuscular Junction
Authors: Shahrezaei Vahid , Cao Alex , Delaney Kerry R.
Published: December 2006

Neurotransmitter release is triggered by the cooperative action of approximately five Ca2+ions entering the presynaptic terminal through Ca2+channels. Depending on the organization of the active zone (AZ), influx through one or many channels may be needed to cause fusion of a vesicle. Using a combination of experiments and modeling, we examined the number of channels that contribute Ca2+for fusion of a single vesicle in a frog neuromuscular AZ. We compared Ca2+influx to neurotransmitter release by measuring presynaptic action potential-evoked (AP-evoked) Ca2+transients simultaneously with postsynaptic potentials. Ca2+influx was manipulated by changing extracellular [Ca2+] (Caext) to alter the flux per channel or by reducing the number of open Ca2+channels with ω-conotoxin GVIA (ω-CTX). When Caextwas reduced, the exponent of the power relationship relating release to Ca2+influx was 4.16 ± 0.62 (SD;n= 4), consistent with a biochemical cooperativity of ∼5. In contrast, reducing influx with ω-CTX yielded a power relationship of 1.7 ± 0.44 (n= 5) for Caextof 1.8 mmand 2.12 ± 0.44 for Caextof 0.45 mm(n= 5). Using geometrically realistic Monte Carlo simulations, we tracked Ca2+ions as they entered through each channel and diffused in the terminal. Experimental and modeling data were consistent with two to six channel openings per AZ per AP; the Ca2+that causes fusion of a single vesicle originates from one or two channels. Channel cooperativity depends mainly on the physical relationship between channels and vesicles and is insensitive to changes in the non-geometrical parameters of our model.
Neural Correlates of Vibrotactile Working Memory in the Human Brain
Authors: Preuschhof Claudia , Heekeren Hauke R. , Taskin Birol , Schubert Torsten , Villringer Arno
Published: December 2006

Recent neurophysiological studies in macaques identified a network of brain regions related to vibrotactile working memory (WM), including somatosensory, motor, premotor, and prefrontal cortex. In these studies, monkeys decided which of two vibrotactile stimuli that were sequentially applied to their fingertips and separated by a short delay had the higher vibration frequency. Using the same task, the objective of the present study was to identify the neural correlates related to the different task periods (encoding, maintenance, and decision making) of vibrotactile WM in the human brain. For this purpose, we used event-related functional magnetic resonance imaging and contrasted WM trials with a control condition of vibrotactile stimulation that did not require maintenance and decision making. We found that vibrotactile WM has a similar but not identical neural organization in humans and monkeys. Consistent with neurophysiological data in monkeys and behavioral studies in humans, the primary somatosensory and the ventral premotor cortex exhibited increased activity during encoding. Maintenance of a vibrotactile memory trace evoked activity in the premotor and ventrolateral prefrontal cortex. Decision making caused activation in the somatosensory, premotor, and lateral prefrontal cortex. However, human vibrotactile WM recruited additional areas. Decision making activated a broader network than that studied thus far in monkeys. Maintenance and decision making additionally activated the inferior parietal lobe. Although the different task components evoked activity in distinctive neural networks, there was considerable overlap of activity, especially regarding maintenance and decision making, indicating that similar neural mechanisms are required for the subprocesses related to these task components.
Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain
Authors: Jhaveri Maulik D. , Richardson Denise , Kendall David A. , Barrett David A. , Chapman Victoria
Published: December 2006

Cannabinoid-based medicines have therapeutic potential for the treatment of pain. Augmentation of levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is analgesic in models of acute and inflammatory pain states. The aim of this study was to determine whether local inhibition of FAAH alters nociceptive responses of spinal neurons in the spinal nerve ligation model of neuropathic pain. Electrophysiological studies were performed 14–18 d after spinal nerve ligation or sham surgery, and the effects of the FAAH inhibitor cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597) on mechanically evoked responses of spinal neurons and levels of endocannabinoids were determined.

Intraplantar URB597 (25 μg in 50 μl) significantly (p< 0.01) attenuated mechanically evoked responses of spinal neurons in sham-operated rats. Effects of URB597 were blocked by the cannabinoid 1 receptor (CB1) antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] (30 μg in 50 μl) and the opioid receptor antagonist naloxone. URB597 treatment increased levels of anandamide, 2-arachidonyl glycerol, and oleoyl ethanolamide in the ipsilateral hindpaw of sham-operated rats. Intraplantar URB597 (25 μg in 50 μl) did not, however, alter mechanically evoked responses of spinal neurons in spinal nerve ligated (SNL) rats or hindpaw levels of endocannabinoids. Intraplantar injection of a higher dose of URB597 (100 μg in 50 μl) significantly (p< 0.05) attenuated evoked responses of spinal neurons in SNL rats but did not alter hindpaw levels of endocannabinoids. Spinal administration of URB597 attenuated evoked responses of spinal neurons and elevated levels of endocannabinoids in sham-operated and SNL rats. These data suggest that peripheral FAAH activity may be altered or that alternative pathways of metabolism have greater importance in SNL rats.
Preference for Immediate over Delayed Rewards Is Associated with Magnitude of Ventral Striatal Activity
Authors: Hariri Ahmad R. , Brown Sarah M. , Williamson Douglas E. , Flory Janine D. , de Wit Harriet , Manuck Stephen B.
Published: December 2006

Discounting future outcomes as a function of their deferred availability underlies much of human decision making. Discounting, or preference for immediate over delayed rewards of larger value, is often associated with impulsivity and is a risk factor for addictive disorders such as pathological gambling, cigarette smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in mediating behavioral responses and physiological states associated with reward, and dysregulation of the VS contributes to addiction, perhaps by affecting impulsive decision-making. Behavioral tests of delay discounting (DD), which index preference for smaller immediate over larger delayed rewards, covary with impulsive tendencies in humans. In the current study, we examined the relationship between individual differences in DD, measured in a behavioral assessment, and VS activity measured with blood oxygenation level-dependent functional magnetic resonance imaging, in 45 adult volunteers. VS activity was determined using a task involving positive and negative feedback with monetary reward. Analyses revealed that individual differences in DD correlate positively with magnitude of VS activation in response to both positive and negative feedback, compared with a no-feedback control condition. Variability in DD was also associated with differential VS activation in response to positive, compared with negative, feedback. Collectively, our results suggest that increased preference for smaller immediate over larger delayed rewards reflects both a relatively indiscriminate and hyper-reactive VS circuitry. They also highlight a specific neurocognitive mechanism that may contribute to increased risk for addiction.
Mechanisms of Efferent-Mediated Responses in the Turtle Posterior Crista
Authors: Holt Joseph C. , Lysakowski Anna , Goldberg Jay M.
Published: December 2006

To study the cellular mechanisms of efferent actions, we recorded from vestibular-nerve afferents close to the turtle posterior crista while efferent fibers were electrically stimulated. Efferent-mediated responses were obtained from calyx-bearing (CD, calyx and dimorphic) afferents and from bouton (B) afferents distinguished by their neuroepithelial locations into BT units near the torus and BM units at intermediate sites. The spike discharge of CD units is strongly excited by efferent stimulation, whereas BT and BM units are inhibited, with BM units also showing a postinhibitory excitation. Synaptic activity was recorded intracellularly after spikes were blocked. Responses of BT/BM units to single efferent shocks consist of a brief depolarization followed by a prolonged hyperpolarization. Both components reflect variations in hair-cell quantal release rates and are eliminated by pharmacological antagonists of α9/α10 nicotinic receptors. Blocking calcium-dependent SK potassium channels converts the biphasic response into a prolonged depolarization. Results can be explained, as in other hair-cell systems, by the sequential activation of α9/α10 and SK channels. In BM units, the postinhibitory excitation is based on an increased rate of hair-cell quanta and depends on the preceding inhibition. There is, in addition, an efferent-mediated, direct depolarization of BT/BM and CD fibers. In CD units, it is the exclusive efferent response. Nicotinic antagonists have different effects on hair-cell efferent actions and on the direct depolarization of CD and BT/BM units. Ultrastructural studies, besides confirming the efferent innervation of type II hair cells and calyx endings, show that turtle efferents commonly contact afferent boutons terminating on type II hair cells.
Previous Experience with Behavioral Control over Stress Blocks the Behavioral and Dorsal Raphe Nucleus Activating Effects of Later Uncontrollable Stress: Role of the Ventral Medial Prefrontal Cortex
Authors: Amat José , Paul Evan , Zarza Christina , Watkins Linda R. , Maier Steven F.
Published: December 2006

Previous experience with stressors over which the subject has behavioral control blocks the typical behavioral consequences of subsequent exposure to stressors over which the organism has no behavioral control. The present experiments explored the involvement of the ventral medial prefrontal cortex (mPFCv) in mediating this “immunizing” or resilience producing effect of an initial experience with control. Behavioral immunization was blocked by inactivation of the mPFCv with muscimol at the time of the initial experience with control, as well as at the time of the later exposure to uncontrollable stress. Inhibition of protein synthesis within the mPFCv by anisomycin also blocked immunization when administered at the time of the initial controllable stress but had no effect when administered at the time of the later uncontrollable stress. Additional experiments found that the initial experience with control blocks the intense activation of serotonergic cells in the dorsal raphe nucleus that would normally be produced by uncontrollable stress, providing a mechanism for behavioral immunization. Furthermore, mPFCv activity during the initial controllable stressor was required for this effect to occur. These results suggest that the mPFCv is needed both to process information about the controllability of stressors and to utilize such information to regulate responses to subsequent stressors. Moreover, the mPFCv may be a site of storage or plasticity concerning controllability information. These results are consistent with recent research in other domains that explore the functions of the mPFCv.