bluuebunny/crossref_metadata_2025 huggingface dataset:
Two New Species of Epistylis (Ciliophora: Peritrichida) on the Blue Crab (Callinectes sapidus) in the Gulf of Mexico
Authors: MA HONGWEI , OVERSTREET ROBIN M.
Published: January 2006

ABSTRACT. Two epibiotic peritrichs infested the blue crab, Callinectes sapidus, from the Gulf of Mexico, Mississippi, USA. Epistylis callinectes n. sp. was isolated from the epipods of maxillipeds, bases of gill‐cleaning setae, and gills, and Epistylis clampi n. sp. was isolated from the exterior surfaces of the exoskeleton. Epistylis callinectes has short, symmetrically and dichotomously branched stalks; its zooid is elongate ovoid and conspicuously longer than the individual stalk branches, measuring 40–57 (49) × 18–33 (26) μm in vivo and containing a thick, undivided peristomial lip (PL). It has a single contractile vacuole and a transverse horseshoe‐shaped macronucleus. Its haplokinety (H) and polykinety (Po) complete one and one‐half circuits on the peristome before entering the infundibulum. There is a distal kinetal fragment present at the distal end of both the H and Po. Epistylis callinectes has 48–70 transverse silverlines from the oral area to the trochal band (TB) and 19–26 from the TB to the scopula. Epistylis clampi has long, asymmetrically, and dichotomously branched stalks. Its zooid is elongate vase‐shaped, measuring 35–64 (48) × 21–30 (27) μm in vivo and with a thick, transversely folded PL. The stalks supporting zooids are unequal in length. Its zooid has a single contractile vacuole and a transverse horseshoe‐shaped macronucleus occurs in the upper half of the body. Its H and Po complete approximately one circuit around the peristome before entering the infundibulum. There is a distal kinetal fragment present at the distal end of both the H and Po. This species has 71–112 transverse silverlines from the peristome to the scopula.
Norepinephrine stimulates calprotectin expression in human monocytic cells
Authors: Suryono  , Kido Jun‐ichi , Hayashi Noriko , Kataoka Masatoshi , Shinohara Yasuo , Nagata Toshihiko
Published: January 2006

Background and objective:  Calprotectin is composed of two proteins, S100A8 and S100A9, which are S100 family members, and is detected in gingival crevicular fluid and gingival tissue with inflammation. The release and production of calprotectin are regulated by lipopolysaccharides of periodontopathic bacteria and cytokines. Emotional or psychological stress, a risk factor of periodontal disease, is transmitted by stress modulators including norepinephrine and cortisol. The aim of the present study was to investigate the effect of stress on calprotectin expression using norepinephrine and cortisol.

Methods:  U‐937 cells, a human monocytic cell line, were incubated with norepinephrine in the presence or absence of β‐ or α‐adrenergic receptor antagonists, or with cortisol. The expression of S100A8/S100A9 mRNAs was examined by northern blotting and the amount of calprotectin was measured by enzyme‐linked immunosorbent assay (ELISA). The DNA binding activity of C/EBPα (CCAAT enhancing binding protein), a transcription factor, was examined by electrophoretic mobility shift assay.

Results:  Norepinephrine stimulated the expression of S100A8/S100A9 mRNAs via β‐adrenergic receptors in U‐937 cells and significantly increased calprotectin production to about 3.6‐fold that of the control. However, cortisol had no effect on calprotectin expression at the mRNA and protein levels. Norepinephrine elevated C/EBPα DNA binding activity, but cortisol did not increase the activity.

Conclusion:  Norepinephrine, a stress modulator, stimulated calprotectin expression in human monocytic cells. Calprotectin expression may be regulated by stress in addition to inflammatory factors.
Radiotherapie des Basalzellkarzinoms im Gesichts‐/Kopfbereich: Bedeutung einer niedrigen Einzeldosis für das Langzeitsergebnis
Authors: Olschewski Thomas , Bajor Katharina , Lang Birgit , Lang Eugen , Seegenschmiedt Michael H.
Published: January 2006

Hintergrund: Die Radiotherapie spielt eine wichtige Rolle in der Behandlung des Basalzellkarzinoms des Gesichts‐/Kopfbereichs und erreicht Heilungsraten von 92‐96 %. Verschiedene Radiotherapie‐Fraktionierungsschemata sind beschrieben worden. Die vorliegende Arbeit untersucht die Wirksamkeit und (akute und chronische) Nebenwirkungen eines moderat hypofraktionierten Bestrahlungsschemas.

Patienten und Methodik: 85 Patienten mit 104 Tumoren erhielten eine Radiotherapie bei einem Basalzellkarzinom des Gesichts‐/Kopfbereiches. In 95 % aller Patienten erfolgte eine Fraktionierung von 5x3 Gray/Woche bis zu einer Gesamtdosis von 57 Gray. Untersucht wurden akute und späte Radiotherapie‐Nebenwirkungen sowie das kosmetische Ergebnis.

Ergebnisse: Es wurde kein Lokalrezidiv beobachtet. In 87 % aller Tumoren fanden sich zum Bestrahlungsende nur geringgradige akute Nebenwirkungen. Spätnebenwirkungen waren bei den meisten Patienten ebenfalls geringgradig ausgeprägt. In 94 % aller Tumoren konnte ein “exzellentes” oder “gutes” kosmetisches Ergebnis erreicht werden.

Schlussfolgerungen: Das verwendete Bestrahlungsschema erzielt eine sehr hohe lokale Kontrollrate und (“sehr”) “gute” kosmetische (und funktionelle) Ergebnisse. Die verwendete Fraktionierung kann insgesamt als standardisierte Behandlung für ein Basalzellkarzinom des Gesichts‐/Kopfbereiches empfohlen werden.
Störungen antimikrobieller Lipide bei atopischer Dermatitis
Authors: Melnik Bodo
Published: January 2006

Patienten mit atopischer Dermatitis weisen eine erhöhte Infektanfälligkeit und pathologische Kolonisierung der Haut mit Superantigen sezernierenden Staphylococcus aureus auf. Viel Beachtung fanden in letzter Zeit die antimikrobiellen Peptide, deren Hauptvertreter Cathelicidin und humanes β‐Defensin‐2 bei atopischer Dermatitis vermindert exprimiert werden. Einen wesentlichen Anteil an der Abwehrfunktion der Haut haben aber auch antimikrobiell wirksame Lipide,die vom Stratum corneum ständig bereitgestellt werden. Ziel dieser Arbeit ist es, ein möglichst umfassendes und aktuelles Gesamtbild zur Biochemie und Wirkung antimikrobieller epidermaler Lipide bei atopischer Dermatitis zu präsentieren. Zu den Stratum‐corneum‐Lipiden mit antimikrobieller Wirkung zählen freie Fettsäuren, Glukosylceramide und freie Sphingosine. Verminderte Konzentrationen antimikrobiell wirksamer freier Sphingosine wurden kürzlich bei atopischer Dermatitis beobachtet und mit der pathologischen Staphylococcus aureus‐Kolonisierung in Verbindung gebracht. Das Superantigen Staphylococcus‐Enterotoxin B hemmt bei Patienten mit atopischer Dermatitis die supprimierende Wirkung regulatorischer T‐Zellen auf die T‐Zellproliferation, was zu einer Verstärkung der T‐Zell‐Aktivierung führt. Somit eröffnet die Abtötung Superantigen sezernierender Bakterienstämme durch topische Applikation antimikrobieller Lipide neue antiseptische und immunmodulatorische Möglichkeiten zur Behandlung und Sekundärprävention der atopischen Dermatitis.
Expression and function of agouti signaling protein in cattle
Authors: GRAPHODATSKAYA Daria , JOERG Hannes , ASAI‐COAKWELL Mika , JANETT Fredi , STRANZINGER Gerald
Published: January 2006

Agouti signaling protein (ASIP) is involved in the regulation of pigmentation in mammals by downregulating melanocortin 1 receptor (MC1R) activity. In wild type mice, ASIP is expressed in skin and testes. Widespread tissue expression of ASIP has been found in humans and cattle. Reverse transcription with subsequent real‐time polymerase chain reaction was used to measure ASIP expression levels in skin and five additional tissues from four cattle breeds. The expression of each sample was represented as a percentage of the expression of the housekeeping gene b‐actin. No significant difference was found in the expression levels in skin from Red Holstein, Simmental (red), Holstein (black) and Brown Swiss (brown/gray) breeds, which were all in the range of 0.2–0.3%. Expression in other tissues varied greatly between individuals, ranging from 196% in the heart of a Red Holstein animal to 0% in the liver samples of all four breeds. Additionally, we showed that expression of bovine ASIP in cell culture reduces cyclic adenosine monophosphate production in cells expressing MC1R, suggesting that bovine agouti is able to downregulate MC1R signaling.
Analyses of factors affecting dry matter intake of lactating dairy cows
Authors: MAZUMDER Md. Arifur Rahman , KUMAGAI Hajime
Published: January 2006

An experiment was conducted to analyze feed, climate and animal factors affecting dry matter intake (DMI) in lactating dairy cows. Sixteen lactating Holstein cows, with parity from 1 to 6, were assigned to a feeding trial for 2 years, comprising 31 lactations. The animals were fed Italian ryegrass silage, oat hay, alfalfa hay, beet pulp and three types of concentrate. The data, pooled and classified by stage of lactation, season of lactation and parity were analyzed by stepwise multiple regression to determine the nature and extent of factors affecting DMI. A total of 45 prediction equations for DMI were derived. Energy‐corrected milk yield or milk yield was selected as the primary factor of DMI in all the equations in which the ratio of contribution (R2) varied from 0.26 to 0.67. The dietary concentration of organic cell wall, crude fiber, crude protein, organic b fraction, forage to concentrate ratio, average ambient temperature and temperature–humidity index were selected as the secondary factors affecting DMI for pooled data, late lactation (251–350 days of lactation), summer (June–August), spring (March–May), ≥4th lactation, autumn (September–November) and 3rd lactation, respectively, and improved R2 up to 0.77. Except for an impact of bodyweight in several equations, feed and climatic factors significantly improved prediction equations effectively for data classified in different ways. To estimate DMI accurately in lactating dairy cows, feed and climatic factors should be considered for specific conditions.
Investigation of the Effect of Hyperbaric Oxygen on Experimental Cyclosporine Nephrotoxicity
Authors: Atasoyu Enes Murat , Yildiz Senol , Cimsit Maide , Cermik Hakan , Qyrdedi Tauland , Evrenkaya T. Rifki , Aktas Samil , Uzun Gunalp , Bilgi Oguz , Gultepe Mustafa
Published: January 2006

Abstract: Hyperbaric oxygen interacts with drugs which patients use concurrently with hyperbaric oxygen treatment, which may cause in potentiation or inhibition of both therapeutic and toxic effects. We examined the effect of hyperbaric oxygen therapy on experimental cyclosporine A nephrotoxicity. The study comprised four groups of rats: a control group, a cyclosporine A group (25 mg/kg/day intraperitoneally for four days), a hyperbaric oxygen group (60 min. every day for four days at 2.5 atmospheric pressure), and a cyclosporine A+hyperbaric oxygen group (CsA 25 mg/kg/day intraperitoneally for four days+hyperbaric oxygen for 60 min. every day for four days at 2.5 atmospheric pressure). Hyperbaric oxygen did not alter biochemical parameters. Cyclosporine A increased serum urea and serum creatinine levels and decreased creatinine clearance. In the cyclosporine A+hyperbaric oxygen group serum urea level increased more than in the cyclosporine A group. Cyclosporine A increased tubular epithelial cell apoptosis and necrosis score values. The numbers of apoptotic cells in proximal tubule epithelial cells in the cyclosporine A+hyperbaric oxygen group were significantly higher than those of the cyclosporine A group. We recommend that renal functions of the patients receiving cyclosporine A should be monitored during hyperbaric oxygen therapy.
The energetics and environment of the short-GRB afterglows 050709 and 050724
Authors: Panaitescu A.
Published: January 2006

We use the available radio, optical and X-ray measurements for the afterglows of the short bursts 050709 and 050724 to constrain the blast-wave energy, its collimation and the density of the circumburst medium. For GRB 050709 (the duration of which was 0.07 s), we identify two kinds of models: (i) a high-density solution, where the ejecta are collimated in a jet of half-angle θjet > 6° and interact with a medium of particle density 10−4 < n < 0.1 cm−3; and (ii) a low-density solution with θjet > 2° and n < 10−5 cm−3. These density ranges are compatible with those expected in the vicinity of the host galaxy and in the intergalactic medium, lending support to the hypothesis that the progenitor of GRB 050709 is a neutron star–neutron star or neutron star–black hole merger. For GRB 050724 (which lasted 1.5 s), we obtain 0.1 < n < 103 cm−3 and θjet > 8°. The range of allowed densities shows that this burst occurred in the interstellar medium. The dynamical parameters of the high-density model for the GRB afterglow 050709 are similar to those for 050724. If these parameters are representative for short-GRB outflows, then these jets are less collimated and have a lower kinetic energy than those of long bursts, which suggests that GRB jets are not magnetically collimated and are powered by the gravitational energy of the torus. Evidently, the analysis of more short-GRB afterglows is required for a more robust conclusion.
A Light‐Activated β‐Turn Scaffold within a Somatostatin Analog: NMR Structure and Biological Activity
Authors: Ulysse Luckner G. , Chmielewski Jean
Published: January 2006

Somatostatin owes its biological activity to the presence of a well‐defined β‐turn centered around the tetrapeptide Phe‐Trp‐Lys‐Thr. We have developed a light‐activated β‐turn scaffold, 1, with the ability to template a β‐turn conformation within the somatostatin tetrapeptide only upon photolysis. The three‐dimensional structure of the trans cyclic peptide I obtained by NMR revealed no β‐turn conformation; however, when isomerized to the cis form II with light, the solution structure of the resulting cyclic peptide was found to contain a type II′β‐turn within the Phe‐Trp‐Lys‐Thr sequence. Binding assays with the SRIF receptor demonstrated that the cis peptide displayed enhanced affinity for the receptor over the trans form.
The Use of Three‐Dimensional Shape and Electrostatic Similarity Searching in the Identification of a Melanin‐Concentrating Hormone Receptor 1 Antagonist
Authors: Muchmore Steven W. , Souers Andrew J. , Akritopoulou‐Zanze Irini
Published: January 2006

To aid in the identification of novel melanin‐concentrating hormone receptor 1 (MCHr1) antagonists, a unique virtual library of readily synthesized molecules was designed and assembled based on 323 monomer compounds containing reactive moieties in combination with 30 core molecules having diamine functionality. The resulting library of 3 129 870 molecules was searched using three‐dimensional shape similarity measures that were complimented with a novel electrostatic distribution similarity‐matching algorithm. One of the top scoring hits in this library was synthesized and characterized for MCHr1 antagonism, where it exhibited at least a threefold improvement in binding affinity and cellular potency relative to the parent MCHr1 ligand. This work demonstrates that the use of shape and electrostatic similarity matching in combination with a well‐designed virtual library can be used to augment standard medicinal chemistry techniques.
Lack of contribution of P2X receptors to neurally mediated vasoconstriction in the rabbit kidneyin vivo
Authors: Eppel G. A. , Ventura S. , Denton K. M. , Evans R. G.
Published: January 2006

Aim: The contribution of adenosine triphosphate (ATP) to the neural control of regional renal perfusionin vivoremains unknown. We therefore examined whether P2X receptors mediate renal vascular responses to electrical stimulation of the renal nerves (RNS) in pentobarbitone anaesthetized rabbits.

Methods: Responses to RNS were tested before and during renal arterial infusion ofα,β‐methylene ATP (α,β‐mATP, 7–56 μg kg−1 min−1) to desensitize P2X1receptors. RNS consisted of 3 min trains at graded frequencies and short trains of RNS (4–32 pulses).

Results: Three‐minute trains of RNS reduced renal blood flow (RBF), cortical laser Doppler flux (CLDF), and medullary LDF (MLDF) by −90 ± 3%, −89 ± 3% and −31 ± 11%, respectively, at 4 Hz. MLDF was reduced less than CLDF or RBF. During short train RNS, RBF, CLDF and MLDF were reduced by −22 ± 2%, −15 ± 2% and −12 ± 2%, respectively, for 32 s at 1 Hz. CLDF and MLDF were reduced to a similar extent. Infusion ofα,β‐mATP induced transient reductions in RBF, CLDF and MLDF, but within 5 min these variables had recovered to control levels. Vascular responses to RNS were not significantly altered byα,β‐mATP treatment.

Conclusions: In the rabbit kidneyin vivo,α,β‐mATP‐sensitive receptors mediate vasoconstriction and reduce perfusion in both cortical and medullary vascular beds. However, these receptors do not mediate neurally induced reductions in renal perfusion.
Cascading Glia Reactions: a Common Pathomechanism and Its Differentiated Control by Cyclic Nucleotide Signaling
Authors: SCHUBERT PETER , MORINO TADAO , MIYAZAKI HIROFUMI , OGATA TADANORI , NAKAMURA YOICHI , MARCHINI CRISTINA , FERRONI STEFANO
Published: January 2006

Abstract: A pathological glia activation, stimulated by inflammatory proteins, β‐amyloid, or brain ischemia, is discussed as a common pathogenic factor for progressive nerve cell damage in vascular and Alzheimer dementia. A critical point seems to be reached, if the cytokine‐controlled microglial upregulation causes a secondary activation of astrocytes which loose the negative feedback control, are forced to give up their physiological buffering function, and may add to neuronal damage by the release of nitric oxide (NO) and by promoting toxic β‐amyloid formation. A strengthening of the cyclic adenosine‐5′,3′‐monophosphate (cAMP) signaling exerted a differential inhibition of the stimulatory cytokines tumor necrosis factor‐α (TNF‐α and interleukin‐1β (IL‐1β) released from cultured rat microglia, but maintained the negative feedback signal IL‐6; cAMP inhibited also the release of free oxygen radicals (OR) but not of NO. Reinforcement of the NO‐induced cyclic guanosine monophosphate (cGMP) increase by blockade of the phosphodiesterase (PDE) subtype‐5 with propentofylline counterbalanced the toxic NO action that causes with OR neuronal damage by peroxynitrate formation. In rat cultured astrocytes, a prolonged cAMP elevation favored cell differentiation, the expression of a mature ion channel patter, and an improvement of the extracellular glutamate uptake. Cyclic AMP signaling could be strengthened by PDE blockade and by raising extracellular adenosine, which stimulates A2 receptor‐mediated cAMP synthesis. Via an A1 receptor‐mediated effect, elevated adenosine was found to overcome a deficient intracellular calcium mobilization resulting from an impaired muscarinic signaling at pathologically decreased acetylcholine concentrations. We suggest that pharmaca, which elevate extracellular adenosine and/or block the degradation of cyclic nucleotides, may be used to counteract glia‐related neuronal damage in dementing processes.
Cerebrovascular Pathology in Alzheimer's Disease and Leukoaraiosis
Authors: BROWN WILLIAM R. , MOODY DIXON M. , THORE CLARA R. , CHALLA VENKATA R.
Published: January 2006

Abstract: A high percentage of patients with Alzheimer's disease (AD) show evidence of white matter degeneration known as leukoaraiosis (LA), which is due to chronic ischemia. We found that the periventricular veins tend to become occluded by multiple layers of collagen in the vessel walls in the elderly. This collagen deposition is particularly excessive in LA lesions. Therefore, it is present in the brains of many AD patients, along with other ischemia‐causing cerebrovascular pathology. We found evidence that there is severe loss of oligodendrocytes in LA, due to extensive apoptosis. No evidence of inflammation was found in the LA lesions. In thick celloidin sections of AD brain, we have obtained detailed 3D views of small (early) deposits of amyloid (stained with β‐amyloid antibody) around capillaries (stained with collagen IV antibody).
Similar Ultrastructural Breakdown of Cerebrocortical Capillaries in Alzheimer's Disease, Parkinson's Disease, and Experimental Hypertension: What is the Functional Link?
Authors: FARKAS ESZTER , DE JONG GINEKE I. , APRÓ ETELKA , DE VOS ROB A.I. , JANSEN STEUR ERNST N.H. , LUITEN PAUL G.M.
Published: January 2006

Abstract: The brain, as an intensely active organ, is highly dependent on a sufficient nutrient and oxygen availability in order to reach its optimal working capacity. It is well known that the vital supply of energy substrates is provided by the circulatory system, which splits up into a fine, terminal capillary network in target tissues. These capillaries are considered as important sites, since the actual nutrient trafficking takes place through their walls. That is why an intact, preserved structure of the microvessels is crucial to fulfill their function. Since the brain is known to be particularly vulnerable to suboptimal oxygen and glucose delivery, the intact morphology of capillaries is of paramount importance.

Several observations have indicated that the cerebral capillary ultrastructure is damaged in Alzheimer's disease (AD). Curiously, the regional cerebral blood flow of AD patients is also significantly lower than in age‐matched control individuals. Based on these data, it has been suggested that the decreased blood supply and the cerebrovascular alterations contribute to the development of dementia. However, we have observed similar capillary damage in Parkinson's disease patients and chronically hypertensive rats in addition to AD cases, as presented here. These findings indicate that cerebral capillary damage is not exclusive for AD but occurs under other neurodegenerative disorders and hypertension, as well. We hypothesize that ultrastructural abnormalities of cerebral capillaries are causally related to decreased cerebral blood flow and create a condition that favors neurodegenerative mechanisms including the development of dementia.
Distribution of Amyloid β42 in Relation to the Cerebral Microvasculature in an Elderly Cohort with Alzheimer's Disease
Authors: THOMAS A. J. , MORRIS C. M. , FERRIER I. N. , KALARIA R. N.
Published: January 2006

Abstract: Amyloid β (Aβ) deposits and neurofibrillary pathology are characteristic features of Alzheimer's disease (AD). The association of Aβ with cerebral vessels is an intriguing feature of AD. While some degree of cerebral Aβ angiopathy involving the leptomeninges and intraparenchymal vessels occurs in almost all cases of AD, the proportion of microvessels within a neocortical region containing deposits of Aβ peptide is not known. In this study, we examined a cohort of clinically and pathologically evaluated AD cases to assess the percentage of cerebral microvessels in the temporal cortex and parahippocampal gyrus associated with the predominant, Aβ42 form of the peptide. We also assessed whether the distribution and burden of amyloid was related to apolipoprotein E (APOE) genotype. Using double immunostaining methods, we surprisingly found that at least 40% of the microvessels in the two brain regions contained Aβ42 deposits. There was no correlation of such localization with APOE genotype, however, ɛ4 homozygotes revealed a greater burden of Aβ40. These observations suggest that high proportions of cortical microvessels are associated with Aβ42, which may affect microvascular function.
Which Vascular Lesions Are of Importance in Vascular Dementia?
Authors: ESIRI MARGARET M.
Published: January 2006

Abstract: Most necropsy surveys of dementia have found that vascular disease is second only to alzheimer's disease as a cause of dementia. Alzheimer's disease and cerebrovascular disease also often coexist. The purpose of the present study was to determine the nature of the cerebrovascular lesions that are most significant in producing dementia. These were analyzed in a group of cases of dementia in which only vascular pathology was present and, in particular, no more than trivial amounts of alzheimer‐type pathology were present. The cerebrovascular lesions in this group of cases were compared with those in a group of stroke cases who were nondemented and a group of elderly cases without stroke or dementia. Severe cribriform change and deep white/grey matter microinfarcts were significantly more common in the test group than in either of the control groups, whereas single macroscopic infarcts were more common in the stroke control group than either of the other two groups. Thus, microvascular deep white and grey matter lesions, but not macroscopic infarction, were significant in vascular dementia. The results of this study will be discussed in relation to the view that microvascular lesions may also contribute to dementia in subjects with more extensive alzheimer‐type pathology and thus lower the threshold at which alzheimer‐type pathology becomes clinically manifest.
Limitations of Clincal Criteria for the Diagnosis of Vascular Dementia in Clinical Trials: Is a Focus on Subcortical Vascular Dementia a Solution?
Authors: ERKINJUNTTI TIMO , INZITARI DOMENICO , PANTONI LEONARDO , WALLIN ANDERS , SCHELTENS PHILIP , ROCKWOOD KENNETH , DESMOND DAVID W.
Published: January 2006

Abstract: Vascular dementia (VaD) includes several different vascular mechanisms and changes in the brain, and has different causes and clinical manifestations. Critical to its conceptualization and diagnosis are definitions of the cognitive syndrome, vascular etiologies, and changes in the brain. Variation in these has resulted in different definitions of VaD, estimates of prevalence, and types and distribution of brain lesions. This defintional heterogeneity may have been a factor for negative results in prior clinical trials on VaD. We propose that the division of VaD into subtypes can identify a more homogenous group of patients for drug trials. A so‐called “subcortical” VaD could incorporate two old clinical entities “Binswanger's disease” and “the lacunar state.” Small vessel disease is the primary vascular etiology, lacunar infarcts and ischemic white matter lesions are the primary type of brain lesions, the subcortical areas and frontal connections are the primary location of lesions, and a subcortical syndrome as the primary clinical manifestation. The clinical syndromes are likely more variable, and urgently need to be categorized. Selection of these patients for clinical trials could mainly be based on brain imaging features, where the essential changes and the main aspects of the lesions include extensive ischemic white matter lesions and lacunar infarcts in the deep gray and white matter structures. Subcortical VaD is expected to show a more predictable clinical picture, natural history, outcomes, and treatment responses.
Linear Relation between Cerebral Phosphocreatine Concentration and Memory Capacities during Permanent Brain Vessel Occlusions in Rats
Authors: PLASCHKE KONSTANZE , YUN SEONG‐WOOK , MARTIN EIKE , HOYER SIEGFRIED , BARDENHEUER HUBERT J.
Published: January 2006

Abstract: The present study investigates the interrelation between cerebral energy state and memory capacities in a rat model of stepwise cerebral vessel occlusions. After acute and subchronic permanent vessel occlusions, cortical energy metabolites (ATP, phosphocreatine, ADP, AMP) were detected by high‐pressure liquid chromatography (HPLC) analysis, and the effects on learning, memory, and cognitive behavior were evaluated using a holeboard test. The results of the study demonstrated a drastic decrease in energy‐rich phosphates by 33% for phosphocreatine and by 44% for ATP after acute vessel occlusions. In addition, rat working and reference memories were strikingly decreased to about 5% of controls. In contrast, two weeks after four‐vessel occlusion, the energy state was almost completely restored to control levels. However, a significant decrease in memory capacities was observed in subchronic state. In summary, this study has demonstrated a close linear relationship (p < 0.001) between an impaired cerebral energy state and brain memory dysfunction after acute and permanent cerebral four‐vessel occlusion. Thus, this animal model of stepwise reduction of the cerebral blood supply may reflect some clinically relevant processes occurring during cerebrovascular and neurodegenerative diseases.
Animal Model of Alzheimer‐like Vascular Pathology and Inflammatory Reaction
Authors: RHODIN J. , THOMAS T. , BRYANT M. , SUTTON E. T.
Published: January 2006

Abstract: This in vivo animal model of vascular inflammatory reaction facilitates morphologic and hemodynamic analyses of leukocyte‐endothelial interaction and can be monitored by video microscopy and electron microscopy. The model has served as a rapid means to explore the deleterious vascular actions and inflammatory response to the cytokines tumor necrosis factor, interleukin‐1 and amyloid‐β, as well as the protective effects of superoxide dismutase, estrogen, and cytokine antagonists.
Cortical Cholinergic Denervation Elicits Vascular Aβ Deposition
Authors: ROHER ALEX E. , KUO YU‐MIN , POTTER PAMELA E. , EMMERLING MARK R. , DURHAM ROBERT A. , WALKER DOUGLAS G. , SUE LUCIA I. , HONER WILLIAM G. , BEACH THOMAS G.
Published: January 2006

Abstract:Selective destruction of the cholinergic nucleus basalis magnocellularis (nbm) in the rabbit by the p75 neurotrophin receptor (NTR) immunoglobulin G (IgG) complexed to the toxin saporin leads to the deposition of amyloid‐beta (Aβ) in and around cerebral blood vessels. In some instances, the perivascular Aβ resemble the diffuse deposits observed in Alzheimer's disease (AD). We propose that cortical cholinergic deprivation results, among other perturbations, in the loss of vasodilation mediated by acetylcholine. In addition to a dysfunctional cerebral blood flow, alterations in vascular chemistry affecting endothelial and smooth muscle cells may result in cerebral hypoperfusion and a breached blood‐brain barrier (BBB). The selective removal of the rabbit nbm and Aβ accumulation may serve as an important nontransgenic, and more physiological, model for the testing of pharmacological and immunological agents designed to control the deposition and the deleterious effects of Aβ in AD.
Effect of a Memory‐Enhancing Drug, AIT‐082, on the Level of Synaptophysin
Authors: LAHIRI D. K , GE Y.‐W. , FARLOW M. R.
Published: January 2006

Abstract: Our objective is to study the effect of AIT‐082 on the level of synaptophysin in cultured pheochromocytoma (PC12) cells. The drug AIT‐082, a unique purine hypoxanthine derivative, is under development for the treatment of Alzheimer's disease (AD). We analyzed synaptophysin protein as an index of synaptic numbers and density and indirectly neuronal transmission. PC12 cells were treated with nerve growth factor (NGF) (50 ng/ml) and/or different doses of AIT‐082 (5–50 ng/ml) obtained from NeoTherapeutics, CA. In the western immunoblots of conditioned media and cell lysates, we detected synaptophysin as 36–40 kDa protein bands. When PC12 cells were treated with NGF and samples were analyzed at 24 or 48 hours after treatment, the secretion of synaptophysin was drastically reduced in the conditioned medium. A significant reduction in the intracellular level of synaptophysin in NGF‐treated samples was also noted. By contrast, when PC12 cells were treated with AIT‐082, the secretion of synaptophysin was increased in the conditioned medium as compared to the control. There was also a significant increase in the intracellular levels of synaptophysin in AIT‐082‐treated cultures. NGF treatment resulted in sympathetic neuronal phenotypes in PC12 cells. As it is known that the immunoreactivity of the synaptophysin protein correlates with the density of the synaptic terminal, our results suggest that treatment by AIT‐082 could enhance neurotransmitter release at the presynaptic terminal, which may play a role in the improvement of cognition seen in AD subjects.
Differentiated Cerebrovascular Effects of Physostigmine and Tacrine in Cortical Areas Deafferented from the Nucleus Basalis Magnocellularis Suggest Involvement of Basalocortical Projections to Microvessels
Authors: PERUZZI PHILIPPE , VON EUW DOMINIQUE , LACOMBE PIERRE
Published: January 2006

Abstract: Cholinesterase inhibitors used to treat Alzheimer's disease according to the principle of cholinergic replacement therapy have proved to be less beneficial than expected. The present study was designed to investigate the cerebrovascular response to physostigmine and tacrine in the experimental model of lesioning of the nucleus basalis magnocellularis (NBM), a model involving a cholinergic deficit. Regional cerebral blood flow was measured by the [14C]iodoantipyrine tissue sampling technique in conscious rats infused with i.v. physostigmine (0.2 mg/kg/h), tacrine (8 mg/kg/h), or saline, 3–5 weeks after unilateral lesion of the NBM with ibotenic acid. Physostigmine and tacrine dose‐dependently increased blood flow in most cortical and subcortical regions compared to the control group. However, physostigmine caused smaller blood flow increases in several areas, mostly cortical, of the lesioned compared to the intact hemisphere. The converse was observed with tacrine. A facilitated circulatory response appeared in cortical areas deafferented from the NBM, especially in the frontal cortex. These results provide evidence for distinct NBM‐dependent components of the cortical cerebrovascular effects of physostigmine and tacrine. They suggest the involvement of different cellular postsynaptic targets of the NBM. The physostigmine‐type effects could involve direct projections onto an inhibitory cortical interneuron supersensitized by deafferentation. This arrangement may explain why physostigmine and perhaps other cholinergic agonists are unable to specifically compensate for a deficit in NBM functioning. The tacrine‐type effects presumably involve projections to the mi‐crovasculature, including perivascular astrocytes. The neurovascular junction would be sensitized by deafferentation from the NBM. Our data suggest that the regulatory mechanisms of blood flow originating in the NBM might constitute a target of neurodegenerative processes of Alzheimer's disease.
Alzheimer's Disease and Vascular Dementia: Some Points of Confluence
Authors: AGÜERO‐TORRES HEDDA , WINBLAD BENGT
Published: January 2006

Abstract: The lack of biologic markers for Alzheimer's disease and vascular dementia, the controversy regarding the definition of vascular dementia, and the new evidence of vascular risk factors for Alzheimer's disease suggest that the traditional differentiation between Alzheimer's disease and vascular dementia is no longer very clear. We believe that both vascular and degenerative mechanisms contribute to the development of dementia, especially in very old age. The question of whether they are two independent parallel processes or interacting pathologies needs to be clarified.
Neuroscience of decision making and informed consent: an investigation in neuroethics
Authors: Northoff Georg
Published: January 2006

Progress in neuroscience will allow us to reveal the neuronal correlates of psychological processes involved in ethically relevant notions such as informed consent. Informed consent involves decision making, the psychological and neural processes of which have been investigated extensively in neuroscience. The neuroscience of decision making may be able to contribute to an ethics of informed consent by providing empirical and thus descriptive criteria. Since, however, descriptive criteria must be distinguished from normative criteria, the neuroscience of decision making cannot replace the ethics of informed consent. Instead, the neuroscience of decision making could complement the current ethics, resulting in what can be called neuroethics of informed consent. It is concluded that current progress in the neurosciences could complement and change the way in which we approach ethical problems in neuropsychiatry.
INTEGRATIVE PLANT BIOLOGY: Role of Phloem Long-Distance Macromolecular Trafficking
Authors: Lough Tony J. , Lucas William J.
Published: January 2006

Recent studies have revealed the operation of a long-distance communication network operating within the vascular system of higher plants. The evolutionary development of this network reflects the need to communicate environmental inputs, sensed by mature organs, to meristematic regions of the plant. One consequence of such a long-distance signaling system is that newly forming organs can develop properties optimized for the environment into which they will emerge, mature, and function. The phloem translocation stream of the angiosperms contains, in addition to photosynthate and other small molecules, a variety of macromolecules, including mRNA, small RNA, and proteins. This review highlights recent progress in the characterization of phloem-mediated transport of macromolecules as components of an integrated long-distance signaling network. Attention is focused on the role played by these proteins and RNA species in coordination of developmental programs and the plant's response to both environmental cues and pathogen challenge. Finally, the importance of developing phloem transcriptome and proteomic databases is discussed within the context of advances in plant systems biology.
CONTROL OF THE ACTIN CYTOSKELETON IN PLANT CELL GROWTH
Authors: Hussey Patrick J. , Ketelaar Tijs , Deeks Michael J.
Published: January 2006

Plant cells grow through increases in volume and cell wall surface area. The mature morphology of a plant cell is a product of the differential rates of expansion between neighboring zones of the cell wall during this process. Filamentous actin arrays are associated with plant cell growth, and the activity of actin-binding proteins is proving to be essential for proper cell morphogenesis. Actin-nucleating proteins participate in cell expansion and cell plate formation whereas the recycling of actin monomers is required to maintain actin dynamics and controlled growth. Coordination of actin-binding protein activity and other aspects of cytoskeletal behavior during cell development maintains cohesive cell expansion. Emerging plant signaling networks are proving to be powerful regulators of morphology-shaping cytoskeletal activity, and in this review we highlight current research in actin network regulation.
MicroRNAs AND THEIR REGULATORY ROLES IN PLANTS
Authors: Jones-Rhoades Matthew W. , Bartel David P. , Bartel Bonnie
Published: January 2006

MicroRNAs (miRNAs) are small, endogenous RNAs that regulate gene expression in plants and animals. In plants, these ∼21-nucleotide RNAs are processed from stem-loop regions of long primary transcripts by a Dicer-like enzyme and are loaded into silencing complexes, where they generally direct cleavage of complementary mRNAs. Although plant miRNAs have some conserved functions extending beyond development, the importance of miRNA-directed gene regulation during plant development is now particularly clear. Identified in plants less than four years ago, miRNAs are already known to play numerous crucial roles at each major stage of development—typically at the cores of gene regulatory networks, targeting genes that are themselves regulators, such as those encoding transcription factors and F-box proteins.
BIOLOGY AND BIOCHEMISTRY OF GLUCOSINOLATES
Authors: Halkier Barbara Ann , Gershenzon Jonathan
Published: January 2006

Glucosinolates are sulfur-rich, anionic natural products that upon hydrolysis by endogenous thioglucosidases called myrosinases produce several different products (e.g., isothiocyanates, thiocyanates, and nitriles). The hydrolysis products have many different biological activities, e.g., as defense compounds and attractants. For humans these compounds function as cancer-preventing agents, biopesticides, and flavor compounds. Since the completion of the Arabidopsis genome, glucosinolate research has made significant progress, resulting in near-complete elucidation of the core biosynthetic pathway, identification of the first regulators of the pathway, metabolic engineering of specific glucosinolate profiles to study function, as well as identification of evolutionary links to related pathways. Although much has been learned in recent years, much more awaits discovery before we fully understand how and why plants synthesize glucosinolates. This may enable us to more fully exploit the potential of these compounds in agriculture and medicine.
EVIDENCE FOR ASEISMIC DEFORMATION RATE CHANGES PRIOR TO EARTHQUAKES
Authors: Roeloffs Evelyn A.
Published: January 2006

For ten earthquakes in nonmagmatic settings, there are credible published accounts of pre-earthquake deformation-rate changes lasting hundreds of seconds to more than a decade. Although most M > 7.5 earthquakes have occurred without detectable pre-earthquake deformation, the detection threshold for aseismic deformation remains high, in that aseismic slip with moment equivalent to an M5 earthquake would in most (although not all) cases have been missed. Interseismic deformation rates vary without being followed by earthquakes, and a strain-rate change prior to the 1989 Mw6.9 Loma Prieta, California, earthquake is shown to be similar in size to many other rate changes that have occurred since that time. Most examples of pre-earthquake aseismic deformation lasting hundreds of seconds or more probably originate adjacent to, or downdip of, the seismic rupture plane, rather than within the zone that undergoes seismic failure.
DATES AND RATES: Temporal Resolution in the Deep Time Stratigraphic Record
Authors: Erwin Douglas H.
Published: January 2006

The level of achievable stratigraphic resolution determines the nature of the many ecological, evolutionary, and geological questions for which a reasonable answer may be expected. Advances in correlation techniques and in high-resolution radiometric dating and their integration with the fossil record through quantitative biostratigraphy and potentially orbital cyclicity now allows many questions about rates of geological, geochemical, and evolutionary processes to be extended into deep time.
WATER, MELTING, AND THE DEEP EARTH H2O CYCLE
Authors: Hirschmann Marc M.
Published: January 2006

Hydrous melting driven by changes in H2O storage capacity may occur in a variety of settings in the mantle, including in oceanic basalt sources and in deeper regions above and below the transition zone. The 50–200 ppm H2O in the upper mantle likely derives from a blend of sources that may include residues of hydrous partial melting, either in the deep mantle and/or beneath arcs or oceanic islands. Relative to the large storage capacity in the transition zone, low storage capacities above and below may lead to hydrous melting for material upwelling through 410 km or downwelling through 670 km. The apparently very low storage capacity of the lower mantle (<20 ppm H2O) may force melting even if downwelling rocks have normal upper mantle H2O (50–200 ppm) concentrations. Very low storage capacity in the lower mantle, if verified experimentally, presents a challenge to the view that the H2O-rich sources of oceanic island basalts reside in the lower mantle.
MICROGELS: Old Materials with New Applications
Authors: Das Mallika , Zhang Hong , Kumacheva Eugenia
Published: January 2006

▪ Abstract  This review describes the most recent progress in the use of polymer multiresponsive microgels as central components of advanced, functional colloidal materials. Significant areas of development include the use of microgels as microreactors for templated synthesis of inorganic nanoparticles with predetermined properties, as optically active materials including lenses and photonic crystals, and as primary units in site-specific and controlled drug delivery systems. In the last category, both synthetic and biopolymeric microgels are discussed.
A Catalogue of the Effector Secretome of Plant Pathogenic Oomycetes
Authors: Kamoun Sophien
Published: January 2006

Abstract  The oomycetes form a phylogenetically distinct group of eukaryotic microorganisms that includes some of the most notorious pathogens of plants. Oomycetes accomplish parasitic colonization of plants by modulating host cell defenses through an array of disease effector proteins. The biology of effectors is poorly understood but tremendous progress has been made in recent years. This review classifies and catalogues the effector secretome of oomycetes. Two classes of effectors target distinct sites in the host plant: Apoplastic effectors are secreted into the plant extracellular space, and cytoplasmic effectors are translocated inside the plant cell, where they target different subcellular compartments. Considering that five species are undergoing genome sequencing and annotation, we are rapidly moving toward genome-wide catalogues of oomycete effectors. Already, it is evident that the effector secretome of pathogenic oomycetes is more complex than expected, with perhaps several hundred proteins dedicated to manipulating host cell structure and function.
In vivo measurement of synthesis rate of multiple plasma proteins in humans
Authors: Jaleel Abdul , Nehra Vandana , Persson Xuan-Mai T. , Boirie Yves , Bigelow Maureen , Nair K. Sreekumaran
Published: January 2006

Advances in quantitative proteomics have facilitated the measurement of large-scale protein quantification, which represents net changes in protein synthesis and breakdown. However, measuring the rate of protein synthesis is the only way to determine the translational rate of gene transcripts. Here, we report a technique to measure the rate of incorporation of amino acids from ingested protein labeled with stable isotope into individual plasma proteins. This approach involves three steps: 1) production of stable isotope-labeled milk whey protein, oral administration of this intrinsically labeled protein, and subsequent collection of blood samples; 2) fractionation of the plasma and separation of the individual plasma proteins by a combination of anion exchange high-pressure liquid chromatography and gel electrophoresis; and 3) identification of individual plasma proteins by tandem mass spectrometry and measurement of stable isotopic enrichment of these proteins by gas chromatography-mass spectrometry. This method allowed the measurement of the fractional synthesis rate (FSR) of 29 different plasma proteins by using the same precursor pool. We noted a 30-fold difference in FSR of different plasma proteins with a wide range of physiological functions. This approach offers a tremendous opportunity to study the regulation of plasma proteins in humans in many physiological and pathological states.
Carotid and Aortic Stiffness
Authors: Paini Anna , Boutouyrie Pierre , Calvet David , Tropeano Anne-Isabelle , Laloux Brigitte , Laurent Stéphane
Published: January 2006

Several studies have shown that aortic stiffness was an independent predictor for cardiovascular events. However, data are less consistent concerning carotid stiffness. We analyzed the determinants of the discrepancies between aortic and carotid stiffness in different populations with contrasting cardiovascular risk factors: 94 healthy normotensives (NT), 243 nondiabetic hypertensives (HT), and 126 patients with hypertension and type 2 diabetes (T2D). Aortic stiffness was measured with carotid-femoral pulse wave velocity. Common carotid stiffness was determined from the relative stroke change in diameter (measured with a high-resolution echotracking system) and carotid pulse pressure (measured with applanation tonometry) and was expressed in the same dimensions as pulse wave velocity (m/s). We identified the various factors explaining the discrepancies between aortic and carotid stiffness by multivariate analysis of the residuals of the correlation between aortic and carotid stiffness. The strength of the correlation between aortic and carotid stiffness became weaker as the number of cardiovascular risk factors increased (NT, r
2
=0.41; HT, r
2
=0.16; and T2D, r
2
=0.11), whereas we observed the opposite for the discrepancies (residuals) between aortic and carotid stiffness, of which an increasing part was explained (11% in NT, 22% in HT, and 45% in T2D) primarily by aging. In conclusion, although carotid-femoral pulse wave velocity and carotid stiffness provided similar information on the impact of aging on large artery stiffness in normal subjects, this was not the case for high blood pressure and/or diabetes. In these cases, the aorta stiffened more than the carotid artery with age and other cardiovascular risk factors.