bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrothermal alteration and geochemical dispersion in the regolith at Panglo, Eastern Goldfields, Western Australia
Authors: Scott K. M. , Howard R. W.
Published: July 2011

Cuttings from 22 holes drilled through steeply dipping, weathered shales and volcanics at Panglo, 30 km N of Kalgoorlie, help define mineralogical and geochemical variations around flat-lying supergene Au mineralization within a stripped lateritic profile. The regolith profile contains very saline groundwaters only a few metres below the suface. Ore occurs in saprolite and saprock, below a mottled zone which is generally unconformably overlain by
c.
 0.5 m of fluvial/colluvial sediments. Apart from some surface enrichment associated with pedogenic carbonate, Au is strongly depleted in the saprolite above the supergene ore horizon, and only subeconomic mineralization occurs in the underlying fresh rocks.

The Au mineralization at depth is accompanied by pyrite and elevated Ag, As, Co, Cu, Sn, W and Zn contents and is associated with the destruction of albite and formation of muscovite. In the regolith, supergene Au ore at Panglo occurs in the basal portion of the saprolite and Au maintains its association with these elements because they are incorporated into secondary oxide minerals. These elements are thus useful pathfinders for Au, especially as some (e.g. As and Cu) form substantial dispersion haloes about ore. Although the ore is oxidized, it is still within its original primary hydrothermal alteration zone, characterized by muscovite and peripheral paragonite development, especially in shale sequences. Because these micas are resistant to weathering, their distributions can be readily mapped in the regolith. Alternatively, elevated K and depleted Na, Ba and Sr can be used as lithogeochemical indicators of mineralization in weathered shales. Use of Na in alteration indices is complicated by its presence in halite at Panglo, but K/Ba ratios do identify the relict zones of hydrothermal alteration within the regolith.
Regolith mapping for geochemical exploration in the Yilgarn Craton, Western Australia
Authors: Craig M. A.
Published: July 2011

A sound knowledge of the character and distribution of regolith materials within landscapes, as well as the underlying geology and mineralization, is vital in any comprehensive exploration program.

The fundamental techniques used in regolith mapping in Australia can be traced to mapping in the Yilgarn Craton between the early 1980s and the early 1990s. Regolith mapping techniques have subsequently developed beyond the basic, well-established inventory concepts as a result of improved methodologies over the last twenty years. Regolith mapping now routinely involves multi-dataset integration and analysis of field data within a GIS framework. Landsat Thematic Mapper, HyMap™, radar, gamma ray spectrometry, magnetic surveys, airborne electromagnetic surveys (AEM), geochemistry, geological data and digital elevation models (DEM) are becoming standard datasets consulted during the production of regolith maps. Regolith mapping has been influenced directly by its association with geochemical exploration in the Yilgarn Craton of Western Australia. Regolith maps and databases now routinely include information about the nature and distribution of geochemical sample media, such as for example, surface lag. For printed maps, geochemical sampling-media information is provided directly through inclusion in a standard legend with overprint patterns, a custom legend, or a custom thematic map derived from the initial map data where a variety of styles can be available to show any potential sampling media.
Cambios Familiares y Políticas Públicas en América Latina*
Authors: García Brígida , de Oliveira Orlandina
Published: July 2011

Las transformaciones de las familias latinoamericanas reciben atención creciente en los estudios sociodemográficos, especialmente en aquellos orientados desde una perspectiva de género. En este artículo revisamos los avances en este campo y sopesamos los vínculos entre familias y políticas públicas. Inicialmente nos detenemos en la naturaleza y el significado de las modificaciones en la estructura y dinámica familiares (tamaño, composición, jefatura, tipo y estabilidad de las uniones, división del trabajo y formas de convivencia). Posteriormente, valoramos los encuentros y desencuentros entre cambios familiares e iniciativas gubernamentales; nos centramos en los programas orientados a la conciliación trabajo-familia, y aquellas acciones encaminadas a visibilizar y sancionar la violencia intrafamiliar. Concluimos que a pesar de lo logrado, las acciones son insuficientes. Es preciso complejizar los análisis y las explicaciones, así como impulsar los diseños de indicadores confiables que nos permitan monitorear adelantos, omisiones y el alcance del camino que aún se necesita recorrer.
Molecular determinants of PKA-dependent inhibition of TRPC5 channel
Authors: Sung Tae Sik , Jeon Jae Pyo , Kim Byung Joo , Hong Chansik , Kim Sung Young , Kim Jinsung , Jeon Ju Hong , Kim Hyun Jin , Suh Chang Kook , Kim Seon Jeong , So Insuk
Published: July 2011

Canonical transient receptor potential (TRPC) channels are Ca2+-permeable, nonselective cation channels that are widely expressed in numerous cell types. Here, we demonstrate a new mechanism of TPRC isofom 5 (TRPC5) regulation, via cAMP signaling via Gαs. Monovalent cation currents in human embryonic kidney-293 cells transfected with TRPC5 were induced by G protein activation with intracellular perfusion of GTPγS or by muscarinic stimulation. This current could be inhibited by a membrane-permeable analog of cAMP, 8-bromo-cAMP, by isoproterenol, by a constitutively active form of Gαs [Gαs (Q227L)], and by forskolin. These inhibitory effects were blocked by the protein kinase A (PKA) inhibitors, KT-5720 and H-89, as well as by two point mutations at consensus PKA phosphorylation sites on TRPC5 (S794A and S796A). Surface expression of several mutated versions of TRPC5, quantified using surface biotinylation, were not affected by Gαs (Q227L), suggesting that trafficking of this channel does not underlie the regulation we report. This mechanism of inhibition was also found to be important for the closely related channel, TRPC4, in particular for TRPC4α, although TRPC4β was also affected. However, this form of regulation was not found to be involved in TRPC6 and transient receptor potential vanilloid 6 function. In murine intestinal smooth muscle cells, muscarinic stimulation-induced cation currents were mediated by TRPC4 (>80%) and TRPC6. In murine intestinal smooth muscle cells, 8-bromo-cAMP, adrenaline, and isoproterenol decreased nonselective cation currents activated by muscarinic stimulation or GTPγS. Together, these results suggest that TRPC5 is directly phosphorylated by Gs/cAMP/PKA at positions S794 and S796. This mechanism may be physiologically important in visceral tissues, where muscarinic receptor and β2-adrenergic receptor are involved in the relaxation and contraction of smooth muscles.
Identification and validation of differentially expressed transcripts in a hepatocyte model of cold-induced glycerol production in rainbow smelt (Osmerus mordax)
Authors: Hall Jennifer R. , Clow Kathy A. , Rise Matthew L. , Driedzic William R.
Published: July 2011

Rainbow smelt ( Osmerus mordax ) avoid freezing by producing antifreeze protein (AFP) and accumulating glycerol. Glyceroneogenesis occurs in liver via a branch in glycolysis and gluconeogenesis and is activated by low temperature. Hepatocytes were isolated from the livers of fish acclimated to 8°C. Cells were incubated at warm (8°C; nonglycerol accumulating) or cold (0.4°C; glycerol accumulating) temperature over a 72-h time course. Reciprocal suppression subtractive hybridization libraries enriched for cold-responsive transcripts were constructed at 72 h. Microarray analyses using a 16K salmonid cDNA array were performed at 24, 48, and 72 h. Expression of type II AFP and 21 carbohydrate, amino acid, or lipid metabolism-related transcripts were validated using quantitative RT-PCR. Type II AFP transcript levels were not directly temperature related. In cold cells, levels of the glucose synthesis transcript were transiently higher. Increased glycerol production was not associated with increased phosphofructokinase or cytosolic glycerol-3-phosphate dehydrogenase transcript levels. Levels of transcripts (phosphoenolpyruvate carboxykinase, mitochondrial malate dehydrogenase, alanine aminotransferase, glutamate dehydrogenase, and aquaglyceroporin 9) associated with mobilization of amino acids to fuel glycerol accumulation were all transiently higher, suggesting a common regulatory mechanism. In cold compared with warm cells, pyruvate dehydrogenase kinase [an inhibitor of pyruvate dehydrogenase (PDH)] transcript levels were 20-fold higher. Potent inhibition of PDH would direct pyruvate and oxaloacetate derived from amino acids to glycerol, as opposed to oxidation via the citric acid cycle. Levels of a transcript potentially encoding glycerol-3-phosphatase, an enzyme not yet characterized in any vertebrate species, were higher following cold incubation. Finally, this study also presents the novel finding of increased glutamine synthetase transcript levels in response to low temperature.
E3 ubiquitin-protein ligases in rat kidney collecting duct: response to vasopressin stimulation and withdrawal
Authors: Lee Yu-Jung , Lee Jeong-Eun , Choi Hyo-Jung , Lim Jung-Suk , Jung Hyun Jun , Baek Moon-Chang , Frøkiær Jørgen , Nielsen Søren , Kwon Tae-Hwan
Published: July 2011

The E3 ubiquitin (Ub)-protein ligases (E3s) play a role as regulators of protein trafficking and degradation. We aimed to integrate the profile of E3s in rat kidney and examine the changes in protein abundance of the selected E3s in response to 1-deamino-8-d-arginine vasopressin (dDAVP) stimulation/withdrawal. Sprague-Dawley rats were infused with vehicle ( n = 13), dDAVP for 5 days ( n = 13), or dDAVP was withdrawn for periods (15 min, 30 min, 1, 3, 6, 12, or 24 h) after 5-day infusion ( n = 46). Total RNA was isolated from the inner medulla (IM) for transcriptome analysis. Plasma membrane (PM)- or intracellular vesicle (ICV)-enriched fractions of whole kidney were immunoisolated for liquid chromatography-tandem mass spectrometry analysis. dDAVP infusion for 5 days (D5d) significantly increased urine osmolality, which was maintained during 3-h withdrawal of dDAVP after 5-day infusion (D5d-3h). Consistent with this, aquaporin-2 (AQP2) expression in the PM fractions of D5d and D5d-3h increased, whereas AQP2 expression in the ICV fractions of D5d-3h was further increased, indicating internalization of AQP2. Transcriptome analysis revealed 86 genes of E3s and LC-MS/MS analysis demonstrated 16 proteins of E3s. Among these, seven E3s (BRCA1, UBR4, BRE1B, UHRF1, NEDD4, CUL5, and FBX6) were shared. RT-PCR demonstrated mRNA expressions of the seven identified E3s in the kidney, and immunoblotting demonstrated changes in protein abundance of the selected E3s (BRE1B, NEDD4, and CUL5) in response to dDAVP stimulation/withdrawal or lithium-induced nephrogenic diabetes insipidus. The rate of AQP2 degradation was retarded in mpkCCDc14 cells with small interfering RNA-mediated knockdown of NEDD4 or CUL5. Taken together, identified E3s could be involved in the degradation of proteins associated with vasopressin-induced urine concentration.
Osteopontin deficiency protects against aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney
Authors: Irita Jun , Okura Takafumi , Jotoku Masanori , Nagao Tomoaki , Enomoto Daijiro , Kurata Mie , Desilva Veena Rasika , Miyoshi Ken-ichi , Matsui Yutaka , Uede Toshimitsu , Denhardt David T. , Rittiling Susan R. , Higaki Jitsuo
Published: July 2011

Osteopontin (OPN) has been implicated in the pathology of several renal conditions. Recently, we demonstrated in vitro that aldosterone has important roles in collagen synthesis by inducing OPN (Irita J, Okura T, Kurata M, Miyoshi K, Fukuoka T, Higaki J. Hypertension 51: 507–513, 2008). The aim of the present study was to clarify the roles of OPN in aldosterone-mediated renal fibrosis by infusing aldosterone into either wild-type (WT) or OPN knockout mice (OPN−/−). We used uninephrectomized mice treated with aldosterone and high salt to exacerbate renal fibrosis. After 4 wk of treatment with aldosterone, we showed similar increases in systolic blood pressure in both strains of mice. Urine albumin excretion was greater in aldosterone-infused WT mice than in aldosterone-infused OPN−/−mice. Immunohistochemical analysis showed high levels of OPN expression in aldosterone-infused WT mice. Interstitial fibrosis and inflammatory infiltrations were increased in aldosterone-infused WT mice compared with either vehicle-infused WT or aldosterone-infused OPN−/−mice. These changes were ameliorated markedly by eplerenone treatment in aldosterone-infused WT mice. Aldosterone-infused WT mice also had increased expression of NADPH oxidase subunits compared with aldosterone-infused OPN−/−mice. We observed a marked increase in oxidative stress markers in aldosterone-infused WT mice compared with aldosterone-infused OPN−/−mice. These results indicate that OPN is a promoter of aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney and suggest that inhibition of OPN may be a potential therapeutic target for prevention of renal injury.
Reduced TrkB expression results in precocious age-like changes in neuromuscular structure, neurotransmission, and muscle function
Authors: Kulakowski Scott A. , Parker Sara D. , Personius Kirkwood E.
Published: July 2011

Acute blockade of signaling through the tyrosine kinase receptor B (TrkB) attenuates neuromuscular transmission and fragments postsynaptic acetylcholine receptors (AChRs) in adult mice, suggesting that TrkB signaling is a key regulator of neuromuscular function. Using immunohistochemical, histological, and in vitro muscle contractile techniques, we tested the hypothesis that constitutively reduced TrkB expression would disrupt neuromuscular pre- and postsynaptic structure, neurotransmission, muscle fiber size, and muscle function in the soleus muscle of 6- to 8-mo-old TrkB+/− mice compared with age-matched littermates. Age-like expansion of postsynaptic AChR area, AChR fragmentation, and denervation was observed in TrkB+/− mice similar to that found in 24-mo-old wild-type mice. Neurotransmission failure was increased in TrkB+/− mice, suggesting that these morphologic changes were sufficient to alter synaptic function. Reduced TrkB expression resulted in decreased muscle strength and fiber cross-sectional area. Immunohistochemical and muscle retrograde labeling experiments show that motor neuron number and size are unaffected in TrkB+/− mice. These results suggest that TrkB- signaling at the neuromuscular junction plays a role in synaptic stabilization, neurotransmission, and muscle function and may impact the aging process of sarcopenia.
The action of the canine diaphragm on the lower ribs depends on activation
Authors: De Troyer André
Published: July 2011

Conventional wisdom maintains that the diaphragm lifts the lower ribs during isolated contraction. Recent studies in dogs have shown, however, that supramaximal, tetanic stimulation of the phrenic nerves displaces the lower ribs caudally and inward. In the present study, the hypothesis was tested that the action of the canine diaphragm on these ribs depends on the magnitude of muscle activation. Two experiments were performed. In the first, the C5 and C6 phrenic nerve roots were selectively stimulated in 6 animals with the airway occluded, and the level of diaphragm activation was altered by adjusting the stimulation frequency. In the second experiment, all the inspiratory intercostal muscles were severed in 7 spontaneously breathing animals, so that the diaphragm was the only muscle active during inspiration, and neural drive was increased by a succession of occluded breaths. The changes in airway opening pressure and the craniocaudal displacements of ribs 5 and 10 were measured in each animal. The data showed that 1) contraction of the diaphragm causes the upper ribs to move caudally; 2) during phrenic nerve stimulation, the lower ribs move cranially when the level of diaphragm activation is low, but they move caudally when the level of muscle activation is high and the entire rib cage is exposed to pleural pressure; and 3) during spontaneous diaphragm contraction, however, the lower ribs always move cranially, even when neural drive is elevated and the change in pleural pressure is large. It is concluded that the action of the diaphragm on the lower ribs depends on both the magnitude and the mode of muscle activation. These findings can reasonably explain the apparent discrepancies between previous studies. They also imply that observations made during phrenic nerve stimulation do not necessarily reflect the physiological action of the diaphragm.
Seven days of aerobic exercise training improves conduit artery blood flow following glucose ingestion in patients with type 2 diabetes
Authors: Mikus Catherine R. , Fairfax Seth T. , Libla Jessica L. , Boyle Leryn J. , Vianna Lauro C. , Oberlin Douglas J. , Uptergrove Grace M. , Deo Shekhar H. , Kim Areum , Kanaley Jill A. , Fadel Paul J. , Thyfault John P.
Published: July 2011

The vasodilatory effects of insulin account for up to 40% of insulin-mediated glucose disposal; however, insulin-stimulated vasodilation is impaired in individuals with type 2 diabetes, limiting perfusion and delivery of glucose and insulin to target tissues. To determine whether exercise training improves conduit artery blood flow following glucose ingestion, a stimulus for increasing circulating insulin, we assessed femoral blood flow (FBF; Doppler ultrasound) during an oral glucose tolerance test (OGTT; 75 g glucose) in 11 overweight or obese (body mass index, 34 ± 1 kg/m2), sedentary (peak oxygen consumption, 23 ± 1 ml·kg−1·min−1) individuals (53 ± 2 yr) with non-insulin-dependent type 2 diabetes (HbA1c, 6.63 ± 0.18%) before and after 7 days of supervised treadmill and cycling exercise (60 min/day, 60–75% heart rate reserve). Fasting glucose, insulin, and FBF were not significantly different after 7 days of exercise, nor were glucose or insulin responses to the OGTT. However, estimates of whole body insulin sensitivity (Matsuda insulin sensitivity index) increased ( P < 0.05). Before exercise training, FBF did not change significantly during the OGTT (1 ± 7, −7 ± 5, 0 ± 6, and 0 ± 5% of fasting FBF at 75, 90, 105, and 120 min, respectively). In contrast, after exercise training, FBF increased by 33 ± 9, 39 ± 14, 34 ± 7, and 48 ± 18% above fasting levels at 75, 90, 105, and 120 min, respectively ( P < 0.05 vs. corresponding preexercise time points). Additionally, postprandial glucose responses to a standardized breakfast meal consumed under “free-living” conditions decreased during the final 3 days of exercise ( P < 0.05). In conclusion, 7 days of aerobic exercise training improves conduit artery blood flow during an OGTT in individuals with type 2 diabetes.
Strong interactions between spinal cord networks for locomotion and scratching
Authors: Hao Zhao-Zhe , Spardy Lucy E. , Nguyen Edward B. L. , Rubin Jonathan E. , Berkowitz Ari
Published: July 2011

Distinct rhythmic behaviors involving a common set of motoneurons and muscles can be generated by separate central nervous system (CNS) networks, a single network, or partly overlapping networks in invertebrates. Less is known for vertebrates. Simultaneous activation of two networks can reveal overlap or interactions between them. The turtle spinal cord contains networks that generate locomotion and three forms of scratching (rostral, pocket, and caudal), having different knee-hip synergies. Here, we report that in immobilized spinal turtles, simultaneous delivery of types of stimulation, which individually evoked forward swimming and one form of scratching, could 1) increase the rhythm frequency; 2) evoke switches, hybrids, and intermediate motor patterns; 3) recruit a swim motor pattern even when the swim stimulation was reduced to subthreshold intensity; and 4) disrupt rhythm generation entirely. The strength of swim stimulation could influence the result. Thus even pocket scratching and caudal scratching, which do not share a knee-hip synergy with forward swimming, can interact with swim stimulation to alter both rhythm and pattern generation. Model simulations were used to explore the compatibility of our experimental results with hypothetical network architectures for rhythm generation. Models could reproduce experimental observations only if they included interactions between neurons involved in swim and scratch rhythm generation, with maximal consistency between simulations and experiments attained using a model architecture in which certain neurons participated actively in both swim and scratch rhythmogenesis. Collectively, these findings suggest that the spinal cord networks that generate locomotion and scratching have important shared components or strong interactions between them.
Hydrogen sulfide augments synaptic neurotransmission in the nucleus of the solitary tract
Authors: Austgen James R. , Hermann Gerlinda E. , Dantzler Heather A. , Rogers Richard C. , Kline David D.
Published: July 2011

Within the brain stem, the nucleus tractus solitarii (NTS) serves as a principal central site for sensory afferent integration from the cardiovascular and respiratory reflexes. Neuronal activity and synaptic transmission in the NTS are highly pliable and subject to neuromodulation. In the central nervous system, hydrogen sulfide (H2S) is a gasotransmitter generated primarily by the enzyme cystathionine-β-synthase (CBS). We sought to determine the role of H2S, and its generation by CBS, in NTS excitability. Real-time RT-PCR, immunoblot, and immunohistochemistry analysis identified the presence of CBS in the NTS. Patch-clamp electrophysiology in brain stem slices examined excitatory postsynaptic currents (EPSCs) and membrane properties in monosynaptically driven NTS neurons. Confocal imaging of labeled afferent synaptic terminals in NTS slices monitored intracellular calcium. Exogenous H2S significantly increased the amplitude of evoked solitary tract (TS)-EPSCs, frequency of miniature (m)EPSCs, and presynaptic terminal calcium fluorescence in the NTS. H2S did not alter action potential discharge or postsynaptic properties. On the other hand, the CBS inhibitor aminooxyacetate (AOA) significantly reduced the amplitude of TS-EPSCs and presynaptic terminal calcium fluorescence in the NTS without altering postsynaptic properties. Taken together, these data support a presynaptic role for endogenous H2S in modulation of excitatory neurotransmission in the NTS.
MicroRNAs in Development and Disease
Authors: Sayed Danish , Abdellatif Maha
Published: July 2011

MicroRNAs (miRNAs) are a class of posttranscriptional regulators that have recently introduced an additional level of intricacy to our understanding of gene regulation. There are currently over 10,000 miRNAs that have been identified in a range of species including metazoa, mycetozoa, viridiplantae, and viruses, of which 940, to date, are found in humans. It is estimated that more than 60% of human protein-coding genes harbor miRNA target sites in their 3′ untranslated region and, thus, are potentially regulated by these molecules in health and disease. This review will first briefly describe the discovery, structure, and mode of function of miRNAs in mammalian cells, before elaborating on their roles and significance during development and pathogenesis in the various mammalian organs, while attempting to reconcile their functions with our existing knowledge of their targets. Finally, we will summarize some of the advances made in utilizing miRNAs in therapeutics.
The Dynamic Modulation of GABAAReceptor Trafficking and Its Role in Regulating the Plasticity of Inhibitory Synapses
Authors: Vithlani Mansi , Terunuma Miho , Moss Stephen J.
Published: July 2011

Inhibition in the adult mammalian central nervous system (CNS) is mediated by γ-aminobutyric acid (GABA). The fast inhibitory actions of GABA are mediated by GABA type A receptors (GABAARs); they mediate both phasic and tonic inhibition in the brain and are the principle sites of action for anticonvulsant, anxiolytic, and sedative-hypnotic agents that include benzodiazepines, barbiturates, neurosteroids, and some general anesthetics. GABAARs are heteropentameric ligand-gated ion channels that are found concentrated at inhibitory postsynaptic sites where they mediate phasic inhibition and at extrasynaptic sites where they mediate tonic inhibition. The efficacy of inhibition and thus neuronal excitability is critically dependent on the accumulation of specific GABAAR subtypes at inhibitory synapses. Here we evaluate how neurons control the number of GABAARs on the neuronal plasma membrane together with their selective stabilization at synaptic sites. We then go on to examine the impact that these processes have on the strength of synaptic inhibition and behavior.
Voltage Fluctuations in Neurons: Signal or Noise?
Authors: Yarom Yosef , Hounsgaard Jorn
Published: July 2011

Noise and variability are fundamental companions to ion channels and synapses and thus inescapable elements of brain function. The overriding unresolved issue is to what extent noise distorts and limits signaling on one hand and at the same time constitutes a crucial and fundamental enrichment that allows and facilitates complex adaptive behavior in an unpredictable world. Here we review the growing experimental evidence that functional network activity is associated with intense fluctuations in membrane potential and spike timing. We trace origins and consequences of noise and variability. Finally, we discuss noise-free neuronal signaling and detrimental and beneficial forms of noise in large-scale functional neural networks. Evidence that noise and variability in some cases go hand in hand with behavioral variability and increase behavioral choice, richness, and adaptability opens new avenues for future studies.
Physiological Relevance of Cell Cycle Kinases
Authors: Malumbres Marcos
Published: July 2011

The basic biology of the cell division cycle and its control by protein kinases was originally studied through genetic and biochemical studies in yeast and other model organisms. The major regulatory mechanisms identified in this pioneer work are conserved in mammals. However, recent studies in different cell types or genetic models are now providing a new perspective on the function of these major cell cycle regulators in different tissues. Here, we review the physiological relevance of mammalian cell cycle kinases such as cyclin-dependent kinases (Cdks), Aurora and Polo-like kinases, and mitotic checkpoint regulators (Bub1, BubR1, and Mps1) as well as other less-studied enzymes such as Cdc7, Nek proteins, or Mastl and their implications in development, tissue homeostasis, and human disease. Among these functions, the control of self-renewal or asymmetric cell division in stem/progenitor cells and the ability to regenerate injured tissues is a central issue in current research. In addition, many of these proteins play previously unexpected roles in metabolism, cardiovascular function, or neuron biology. The modulation of their enzymatic activity may therefore have multiple therapeutic benefits in human disease.
Islet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus
Authors: Westermark Per , Andersson Arne , Westermark Gunilla T.
Published: July 2011

Islet amyloid polypeptide (IAPP, or amylin) is one of the major secretory products of β-cells of the pancreatic islets of Langerhans. It is a regulatory peptide with putative function both locally in the islets, where it inhibits insulin and glucagon secretion, and at distant targets. It has binding sites in the brain, possibly contributing also to satiety regulation and inhibits gastric emptying. Effects on several other organs have also been described. IAPP was discovered through its ability to aggregate into pancreatic islet amyloid deposits, which are seen particularly in association with type 2 diabetes in humans and with diabetes in a few other mammalian species, especially monkeys and cats. Aggregated IAPP has cytotoxic properties and is believed to be of critical importance for the loss of β-cells in type 2 diabetes and also in pancreatic islets transplanted into individuals with type 1 diabetes. This review deals both with physiological aspects of IAPP and with the pathophysiological role of aggregated forms of IAPP, including mechanisms whereby human IAPP forms toxic aggregates and amyloid fibrils.
Precipitation and Growth Kinetics in Mechanically Alloyed Ni–Al
Authors: Tang QingXin , Ukai Shigeharu , Minami Akinobu , Hayashi Shigenari
Published: July 2011

The precipitation and growth kinetics ofγ′ precipitates, which are strengthening factors in Ni-base oxide dispersion strengthened (ODS) superalloys, were investigated. The cuboidal-typeγ′ precipitates are formed in conventional arc-melted Ni–Al alloys, whereas spherical-type precipitates are formed in the mechanically alloyed (MAed) specimens. The morphology is controlled by a lattice misfit between theγ′ precipitates and the matrix at the aging temperature of 800°C. The growth kinetics of theγ′ precipitates can be followed by Ostwald ripening. The Arrhenius plot yielded a lower activation energy for the solute atom diffusion in MAed specimens, which is attributed to their high dislocation density and nanosized grains.
Scientific Comparison of Different Online Heart Rate Monitoring Systems
Authors: Schönfelder Martin , Hinterseher Georg , Peter Philipp , Spitzenpfeil Peter
Published: July 2011

Recent technical development focused on real-time heart rate monitoring instead of postexercise evaluation of recorded data. There are several systems on the market that allow direct and real-time monitoring of several individuals at the same time. The present study compared the systems of Polar, Acentas, Activio, and Suunto in a field test with twelve subjects regarding failure quota, operating distance, and ECG validity. Moreover, the installation and use of software and hardware were evaluated with a quality rating system. Chest belts were evaluated with a questionnaire, too. Overall the system of Acentas reached the best mark of all systems, but detailed results showed that every system has its advantages and disadvantages depending on using purpose, location, and weather. So this evaluation cannot recommend a single system but rather shows strength and weakness of all systems and additionally can be used for further system improvements.
The Existence of Multiple Periodic Solutions of Nonautonomous Delay Differential Equations
Authors: Xiao Huafeng , Zheng Bo
Published: July 2011

We study the multiplicity of periodic solutions of nonautonomous delay differential equations which are asymptotically linear both at zero and at
infinity. By making use of a theorem of Benci, some sufficient conditions are obtained to guarantee the existence of multiple periodic solutions.
Multitemporal Satellite Images for Knowledge of the Assyrian Capital Cities and for Monitoring Landscape Transformations in the Upper Course of Tigris River
Authors: Scardozzi Giuseppe
Published: July 2011

The paper is concerned with the contribution that a rich documentation of multitemporal optical satellite images with high resolution provides for the knowledge of the five great Assyrian capital cities (Ashur, Kar-Tukulti-Ninurta, Kalhu, Dur-Sharrukin, and Nineveh, in northern Iraq). These images also allow monitoring changes of landscape in the higher course of the Tigris during the last half century and document damages in archaeological sites during the two Gulf Wars. The data set, available for each city, consists of panchromatic and multispectral images taken between 2001 and 2007 by modern commercial satellites (Ikonos-2, QuickBird-2, and WorldView-1) and of panchromatic photographs of U.S. spy satellites operating between 1965 and 1969 (Corona KH-4B and Gambit KH-7). These photos were taken before diffusion of mechanized agriculture and the expansion of urban areas, so they are very useful to document many archaeological features and the landscape that has been modified in the last decades, as shown by recent satellite images.
Ethanol Extract of Abnormal Savda Munziq, a Herbal Preparation of Traditional Uighur Medicine, Inhibits Caco-2 Cells Proliferation via Cell Cycle Arrest and Apoptosis
Authors: Yusup Abdiryim , Upur Halmurat , Umar Anwar , Berke Benedicte , Moore Nicholas
Published: July 2011

Aims. Study the effect of Abnormal Savda Munziq (ASMq) ethanol extract on the proliferation, apoptosis, and correlative gene, expression in colon cancer cells (Caco-2) to elucidate the molecular mechanisms responsible for the anticancer property of Abnormal Savda Munziq.Materials and Methods. ASMq ethanol extract was prepared by a professional pharmacist. Caco-2 cells were treated with different concentration of ASMq ethanol extract (0.5–7.5 mg/mL) for different time intervals (48 and 72 h). Antiproliferative effect of ASMq ethanol extract was determined by MTT assay; DNA fragmentation was determined by gel electrophoresis assay; cell cycle analysis was detected by flow cytometer; apoptosis-related gene expression was detected by RT-PCR assay.Results. ASMq ethanol extract possesses an inhibition effect on Caco-2 cells proliferation, induction of cell apoptosis, cell cycle arrest in sub-G1 phase, and downregulation of bcl-2 and upregulation of Bax gene expression.Conclusion. The anticancer mechanism of ASMq ethanol extract may be involved in antiproliferation, induction of apoptosis, cell cycle arrest, and regulation of apoptosis-related gene expression such as bcl-2 and Bax activity pathway.
Comparison of Exposure to Selected Cigarette Smoke Constituents in Adult Smokers and Nonsmokers in a European, Multicenter, Observational Study
Authors: Lindner Dirk , Smith Stephen , Leroy Claire Martin , Tricker Anthony R.
Published: July 2011

Background: This multicenter, observational study was conducted in three European countries (Germany, Switzerland, and the United Kingdom) to determine the exposure of adult cigarette smokers and nonsmokers to selected cigarette smoke constituents: 1,3-butadiene, 2-naphthylamine, 4-aminobiphenyl, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrolein, benzene, carbon monoxide, nicotine, pyrene, and o-toluidine.

Methods: Smokers were grouped by tar category (TC) according to the tar yield of their regular cigarette brand: TC1: ≤4 mg tar, TC2: 5–7 mg tar, and TC3: ≥8 mg tar [to the legal tar yield ceiling in the respective countries (10 or 12 mg tar)]. Levels of biomarkers of exposure to the aforementioned cigarette smoke constituents were compared between smokers and nonsmokers, and within smokers across tar categories.

Results: The full population consisted of 1,631 subjects (1,223 smokers and 408 nonsmokers). Biomarkers of exposure were analyzed for 1,558 subjects (valid case population) as follows: 1,159 smokers (TC1: n = 402, TC2: n = 379, TC3: n = 378), and 399 nonsmokers. Exposure levels were higher in smokers than nonsmokers and increased with increasing tar yield and cigarette consumption. An association of tar category and exposure level was observed for all smoke constituents, except pyrene, 4-aminobiphenyl, and o-toluidine, whereas only NNK exposure was different in all three tar categories.

Conclusions: Smoking status and, among smokers, daily cigarette consumption and tar yield were observed to affect biomarker of exposure levels.

Impact: This research provides a comprehensive evaluation of smoke constituent exposure of adult cigarette smokers and nonsmokers in three European countries. Cancer Epidemiol Biomarkers Prev; 20(7); 1524–36. ©2011 AACR.
Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES Is Consistently Increased
Authors: Gonzalez Rachel M. , Daly Don S. , Tan Ruimin , Marks Jeffrey R. , Zangar Richard C.
Published: July 2011

Background: Current biomarkers for breast cancer have little potential for detection. We determined whether breast cancer subtypes influence circulating protein biomarkers.

Methods: A sandwich ELISA microarray platform was used to evaluate 23 candidate biomarkers in plasma samples that were obtained from subjects with either benign breast disease or invasive breast cancer. All plasma samples were collected at the time of biopsy, after a referral due to a suspicious screen (e.g., mammography). Cancer samples were evaluated on the basis of breast cancer subtypes, as defined by the HER2 and estrogen receptor statuses.

Results: Ten proteins were statistically altered in at least one breast cancer subtype, including four epidermal growth factor receptor ligands, two matrix metalloproteases, two cytokines, and two angiogenic factors. Only one cytokine, RANTES, was significantly increased (P < 0.01 for each analysis) in all four subtypes, with areas under the curve (AUC) for receiver operating characteristic values that ranged from 0.76 to 0.82, depending on cancer subtype. The best AUC values were observed for analyses that combined data from multiple biomarkers, with values ranging from 0.70 to 0.99, depending on the cancer subtype. Although the results for RANTES are consistent with previous publications, the multi-assay results need to be validated in independent sample sets.

Conclusions: Different breast cancer subtypes produce distinct biomarker profiles, and circulating protein biomarkers have potential to differentiate between true- and false-positive screens for breast cancer.

Impact: Subtype-specific biomarker panels may be useful for detecting breast cancer or as an adjunct assay to improve the accuracy of current screening methods. Cancer Epidemiol Biomarkers Prev; 20(7); 1543–51. ©2011 AACR.
Comparison of Serum Cotinine Concentration within and across Smokers of Menthol and Nonmenthol Cigarette Brands among Non-Hispanic Black and Non-Hispanic White U.S. Adult Smokers, 2001–2006
Authors: Caraballo Ralph S. , Holiday David B. , Stellman Steven D. , Mowery Paul D. , Giovino Gary A. , Muscat Joshua E. , Eriksen Michael P. , Bernert John T. , Richter Patricia A. , Kozlowski Lynn T.
Published: July 2011

Background: The Food and Drug Administration (FDA) is examining options for regulating menthol content in cigarettes. There are many pharmacologic properties of menthol that may facilitate exposure to tobacco smoke, and it has been suggested that the preference for menthol cigarettes in black smokers accounts for their higher cotinine levels.

Objective: To assess cigarettes smoked per day–adjusted cotinine levels in relation to smoking a menthol or nonmenthol cigarette brand among non-Hispanic black and white U.S. adult smokers under natural smoking conditions.

Method: Serum cotinine concentrations were measured in 1,943 smokers participating in the 2001 to 2006 National Health and Nutrition Examination Surveys (NHANES). The effect of smoking a menthol brand on cigarettes smoked per day–adjusted serum cotinine levels in these two populations was modeled by adjusting for sex, age, number of smokers living in the home, body weight, time since last smoked, and FTC (Federal Trade Commission)-measured nicotine levels. The 8- or 12-digit Universal Product Code (UPC) on the cigarette label was used to determine the cigarette brand and whether it was menthol.

Results: Smoking a menthol cigarette brand versus smoking a nonmenthol cigarette brand was not associated (P ≥ 0.05) with mean serum cotinine concentration in either black or white smokers.

Conclusions: The higher levels of cotinine observed in black smokers compared with white smokers are not explained by their higher preference for menthol cigarette brands.

Impact: Further studies like ours are needed to improve our ability to understand health consequences of future changes in tobacco product design. Cancer Epidemiol Biomarkers Prev; 20(7); 1329–40. ©2011 AACR.
The Impact of Body Mass Index and Physical Activity on Mortality among Patients with Colorectal Cancer in Queensland, Australia
Authors: Baade Peter D. , Meng Xingqiong , Youl Philippa H. , Aitken Joanne F. , Dunn Jeff , Chambers Suzanne K.
Published: July 2011

Background: Few studies have investigated the impact of body mass index (BMI) and physical activity (PA) on mortality among colorectal cancer (CRC) patients and the results are inconsistent. We aimed to examine the impact of these lifestyle factors on all-cause and disease-specific mortality.

Methods: Population-based longitudinal study followed 1,825 patients diagnosed with stages I to III primary CRC during 2003 to 2004 in Queensland, Australia for 5 years. Sociodemographics and clinical characteristics were obtained via questionnaires and medical records.

Results: Participants with some level of PA following diagnosis had 25% to 28% lower risk of all-cause mortality within 5 years of diagnosis than sedentary participants [insufficiently active: HR = 0.72, 95% CI = 0.57–0.91; sufficiently active: HR = 0.75 (0.60–0.94)]; however, the differential for CRC-specific mortality was not significant. Increases in PA from five to 12 months postdiagnosis was associated with reduced CRC-specific mortality by 32% to 36% (increase ≤ 2 hour per week: HR = 0.68 (0.48–0.97); increase > 2 hour per week: HR = 0.64 (0.44–0.93) and 31% for all-cause mortality (increase >2 hour per week: HR = 0.69 (0.50–0.94). Compared with participants with healthy BMI, significant higher mortality risk was observed in underweight patients (all-cause: HR = 2.29 (1.47–3.59); CRC: HR = 1.74 (1.00–3.04), although lower risk in overweight (all-cause: HR = 0.75 (0.61–0.94); CRC: HR = 0.75 (0.59–0.97) and no difference in obese. Excessive weight loss was associated with increased mortality risk by three-fold but no difference in those who gained weight.

Conclusions: Protective effects of being physically active and increasing that activity underlines the importance of interventions to increase activity levels among people being diagnosed with CRC.

Impact: Increased mortality risks associated with being underweight or having weight loss over time is an important indicator for which clinicians, patients, and support personnel can monitor. Cancer Epidemiol Biomarkers Prev; 20(7); 1410–20. ©2011 AACR.
Targeting Src in Mucinous Ovarian Carcinoma
Authors: Matsuo Koji , Nishimura Masato , Bottsford-Miller Justin N. , Huang Jie , Komurov Kakajan , Armaiz-Pena Guillermo N. , Shahzad Mian M.K. , Stone Rebecca L. , Roh Ju Won , Sanguino Angela M. , Lu Chunhua , Im Dwight D. , Rosenshien Neil B. , Sakakibara Atsuko , Nagano Tadayoshi , Yamasaki Masato , Enomoto Takayuki , Kimura Tadashi , Ram Prahlad T. , Schmeler Kathleen M. , Gallick Gary E. , Wong Kwong K. , Frumovitz Michael , Sood Anil K.
Published: July 2011

Purpose: Mucinous ovarian carcinomas have a distinct clinical pattern compared with other subtypes of ovarian carcinoma. Here, we evaluated (i) stage-specific clinical significance of mucinous ovarian carcinomas in a large cohort and (ii) the functional role of Src kinase in preclinical models of mucinous ovarian carcinoma.

Experimental Design: A total of 1,302 ovarian cancer patients including 122 (9.4%) cases of mucinous carcinoma were evaluated for survival analyses. Biological effects of Src kinase inhibition were tested using dasatinib-based therapy in a novel orthotopic mucinous ovarian cancer model (RMUG-S-ip2).

Results: Patients with advanced-stage mucinous ovarian cancer had significantly worse survival than those with serous histology: median overall survival, 1.67 versus 3.41 years, P = 0.002; median survival time after recurrence of 0.53 versus 1.66 years, P < 0.0001. Among multiple ovarian cancer cell lines, RMUG-S-ip2 mucinous ovarian cancer cells showed the highest Src kinase activity. Moreover, oxaliplatin treatment induced phosphorylation of Src kinase. This induced activity by oxaliplatin therapy was inhibited by concurrent administration of dasatinib. Targeting Src with dasatinib in vivo showed significant antitumor effects in the RMUG-S-ip2 model but not in the serous ovarian carcinoma (SKOV3-TR) model. Combination therapy of oxaliplatin with dasatinib further showed significant effects on reducing cell viability, increasing apoptosis, and in vivo antitumor effects in the RMUG-S-ip2 model.

Conclusions: Our results suggest that poor survival of women with mucinous ovarian carcinoma is associated with resistance to cytotoxic therapy. Targeting Src kinase with a combination of dasatinib and oxaliplatin may be an attractive approach for this disease. Clin Cancer Res; 17(16); 5367–78. ©2011 AACR.
Immunosuppression in Patients with High-Grade Gliomas Treated with Radiation and Temozolomide
Authors: Grossman Stuart A. , Ye Xiaobu , Lesser Glenn , Sloan Andrew , Carraway Hetty , Desideri Serena , Piantadosi Steven
Published: July 2011

Purpose: Patients with high-grade gliomas (HGG) routinely receive radiation, temozolomide, and glucocorticoids. As each of these is immunosuppressive, we conducted a prospective, multicenter study to follow CD4 counts over time and determine whether low CD4 counts were associated with adverse outcomes.

Experimental Design: Patients with newly diagnosed HGG had CD4 counts drawn before initiating standard therapy and monthly thereafter for 1 year. Information on hospitalizations, infections, glucocorticoid use, survival, and cause of death were also collected.

Results: Ninety-six evaluable patients were accrued [85% glioblastoma, median age of 57, median Karnofsky performance status (KPS) = 90]. The median CD4 count before radiation and temozolomide treatment was 664 cells/mm3. The CD4 count nadir occurred 2 months after initiating therapy when 73% of patients had CD4 counts less than 300 cells/mm3 and 40% had less than 200 cells/mm3. CD4 counts remained low throughout the year of follow-up. Patients with CD4 counts less than 200 cells/mm3at 2 months had shorter survival than those with higher counts (median: 13.1 vs. 19.7 months, P = 0.002). Median survival was related to CD4 toxicity grades (I = 23.8 months, II = 19.7 months, III–IV = 13.1 months, P = 0.009). The adjusted HR for death attributable to 2-month CD4 count below 200 was 1.66 (P = 0.03). Eighty-eight percent of deaths resulted from disease progression, whereas only 2.5% were due to infection.

Conclusions: Severe reductions in CD4 counts in patients with newly diagnosed HGG treated with radiation and temozolomide treatment are common, treatment-related, long-lasting, and associated with early death from tumor progression. Clin Cancer Res; 17(16); 5473–80. ©2011 AACR.
Haemodiafiltration Does Not Reduce the Frequency of Intradialytic Hypotensive Episodes when Compared to Cooled High-Flux Haemodialysis
Authors: Pinney Jennifer H. , Oates Thomas , Davenport Andrew
Published: July 2011

Introduction: Intradialytic hypotension remains the commonest complication of outpatient haemodialysis (HD) treatments. On-line haemodiafiltration (HDF) has been reported to reduce the frequency of intradialytic hypotension. We introduced on-line HDF into our satellite dialysis program, and prospectively audited the effect of HDF on cardiovascular stability. Methods: 34 patients’ dialysis schedules (Tuesday/Thursday/Saturday) were converted to online post-dilutional HDF, and 44 patients’ dialysis schedules (Monday/Wednesday/Friday) remained on high-flux HD. Blood pressure and intra-treatment complications were monitored prospectively for 12 months. Results: There was no significant change in pre-treatment mean arterial blood pressure in the HDF group during the 12 months of the study (pre-treatment 113.7 ± 0.7 mm Hg vs. 109.3 ± 2.8 after 12 months), or for the HD cohort (113.9 ± 2.7 vs. 117.9 ± 2.6). However, the frequency of intradialytic hypotensive episodes was greater for the HDF cohort: 25.9 versus 16.5% in the HD cohort, p = 0.0116. During HDF, on average >16 litres of substitution fluid was used and the median temperature was 36°C (35°C–36°C), higher than the dialysate in the HD cohort which was 35°C (35°C–36°C), p < 0.05. Conclusion: In this study, HDF did not improve blood pressure control or reduce the frequency of intradialytic hypotensive episodes compared to high-flux HD using cooled dialysate.