bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Cretaceous dinosaur faunas in China: an introduction
Authors: Dong Zhi-Ming
Published: October 2010

Preliminary evidence suggests that during the Early Cretaceous there were separate dinosaur faunas in northern and southern Asia. The northern fauna, the Psittacosaurus fauna, is well known and based upon collections from numerous localities and formations throughout northern China and southern Mongolia. Although the southern fauna is still poorly known and based upon collections from only a small number of sites, it appears to be distinguished by the absence of psittacosaurs. The discovery of Psittacosaurus in Thailand suggests that the division is probably ecological in nature.
The age of the dinosaur-bearing sediments at Tebch, Inner Mongolia, People's Republic of China
Authors: Eberth D. A. , Russell D. A. , Braman D. R. , Deino A. L.
Published: October 2010

The coarsening-upward clastic sequence at Tebch, Inner Mongolia, China, containing the dinosaur Psittacosaurus mongoliensis, comprises the remains of a fluviolacustrine system deposited in an extensional tectonic setting.The presence of Asteropollis sp. cf. Asteropollis trichotomosulcatus (Singh) Singh, 1983 in conjunction with the absence of tricolpate pollen indicates a Barremian or possibly early Aptian age. The overlying Tebch basalt, dated by the 40Ar/39Ar laser step-heating method, yields a mid-Aptian age of 110 ± 0.52 Ma.This chronology supports the argument that the Juifotang Formation of the Jehe Group in western Liaoning is Early Cretaceous, with the Jurassic–Cretaceous boundary very low within, or below, the base of the Jehe Group. Our data also suggest that the Berriasian–Hauterivian (Neocomian) age suggested for the one known Russian locality that has yielded P. mongoliensis (Shestakovskaya Svita at Gorno-Altayaskaya, Avtonomnaya Oblast) may be excessively old.
Ordosemys leios, n.gen., n.sp., a new turtle from the Early Cretaceous of the Ordos Basin, Inner Mongolia
Authors: Brinkman Donald B. , Peng Jiang-Hua
Published: October 2010

Ordosemys leios, n.gen., n.sp., from the Early Cretaceous Luohandong Formation, Zhidan Group, Ordos Basin, Inner Mongolia, is a primitive aquatic turtle with a reduced, fenestrated plastron. It shares with the members of the Centrocryptodira the presence of well-formed articular surfaces on the cervical and caudal vertebrae. Within the Centrocryptodira, characters of the cervical vertebrae suggest it is more closely related to the Polycryptodira than is the Meiolaniidae. Ordosemys shares with the Chelydridae the presence of two procoelous anterior caudals, but this character may be primitive for the Polycryptodira. Characters of the basicranial region of the braincase shared by Ordosemys and the Chelonioidea support a sister-group relationship between these two taxa, but a sister-group relationship between Ordosemys and the Polycryptodira is more strongly supported by characters shared by the Chelonioidea and other members of the Polycryptodira.
New material of Sinemys (Testudines, Sinemydidae) from the Early Cretaceous of China
Authors: Brinkman Donald B. , Peng Jiang-Hua
Published: October 2010

Sinemys lens is redescribed on the basis of new material from the Early Cretaceous of Shandong, China, and a new species of Sinemys from the Ordos Basin in Inner Mongolia is recognized. Sinemys and Manchurochelys are placed in the Sinemydidae (sensu stricto) on the basis of the derived features of a small first suprapygal and an elongate, narrow posterior lobe of the plastron. Sinemys is autapomorphic in the absence of a cervical scute, the entry of the first vertebral onto the anterior margin of the carapace, the absence of a pygal bone, the entry of the fifth vertebral scute into the posterior margin of the carapace, in that the riblike lateral projections of the last three costal bones fit between the adjacent peripherals, and in the isolation of the epiplastra from the hyoplastra by lateral expansion of the entoplastron.Sinemys gamera sp.nov., from the Early Cretaceous Luohandong Formation of the Ordos Basin, Inner Mongolia, is characterized by the presence of a flat carapace with an abbreviated posterior end and the presence of long spines on the seventh costal. The spines in S. gamera may serve a hydrodynamic function.
A new species of stegosaur (Dinosauria) from the Ordos Basin, Inner Mongolia, People's Republic of China
Authors: Dong Zhi-Ming
Published: October 2010

In 1988, an incomplete skeleton of a stegosaurian dinosaur was found in Lower Cretaceous strata of the Ordos Basin of China by the Dinosaur Project (China – Canada – Alberta – Ex Terra). The material includes an articulated series of vertebrae from the last three cervicals to the first five caudals, and the right ilium. The specimen is identified as a new species called Wuerhosaurus ordosensis. It is the only Lower Cretaceous stegosaur known with an articulated series of dorsal vertebrae, which have been reduced to eleven in number.
A Lower Cretaceous enantiornithine bird from the Ordos Basin of Inner Mongolia, People's Republic of China
Authors: Dong Zhi-Ming
Published: October 2010

The discovery of an Early Cretaceous bird from the Ordos Basin of Inner Mongolia (People's Republic of China) is reported. The specimen, collected by the Dinosaur Project (China – Canada – Alberta – Ex Terra) Expedition of 1990, includes scapulocoracoids, humeri, radii, ulnae and metacarpals. It is referred to the Enantiornithes.
Depositional environments and fades transitions of dinosaur-bearing Upper Cretaceous redbeds at Bayan Mandahu (Inner Mongolia, People's Republic of China)
Authors: Eberth D. A.
Published: October 2010

Campanian redbeds near Bayan Mandahu consist of six lithosomes, which in turn comprise twelve lithofacies. The distribution of these lithosomes along a 12 km escarpment resolves into three coeval paleogeographic zones representing a proximal-to-distal depositional gradient. Zone 1, the most proximal, consists of alluvial, lacustrine, and eolian sediments. It is interpreted as an eolian influenced, distal alluvial-fan or braid-plain environment. Farther basinward, zone 2 is dominated by structureless eolian sandstones and caliche profiles with minor occurrences of alluvial, lacustrine, and eolian dune deposits. It is interpreted as a zone of vertically aggrading eolian sand, stabilized by vegetation and a high water table. Zone 3, the most distal, is dominated by eolian dune and structureless eolian deposits with lacustrine and interdune fluvial deposits. It is interpreted as the southern margin of an eolian dune field that was dominated by transverse and barchan dunes. U-shaped, mature caliche profiles can be traced for up to 1.5 km and are abundant throughout zones 2 and 3. They indicate lengthy depositional hiatuses and a swaley paleotopography. Djadokhta Formation paleoenvironments and fossil assemblages in south-central Mongolia compare closely with zones 2 and 3 at Bayan Mandahu, indicating a consistency in climate and depositional processes throughout the Gobi Basin during Campanian times. The depositional environments of modern arid and semiarid basin margins in Central Asia (e.g., Junggar, Tarim) are excellent analogues for the Campanian environments and paleogeography of the Gobi Basin margin.
Khunnuchelys gen.nov., a new trionychid (Testudines: Trionychidae) from the Late Cretaceous of Inner Mongolia and Uzbekistan
Authors: Brinkman Donald B. , Nessov L. A. , Peng Jiang-Hua
Published: October 2010

A new trionychid, Khunnuchelys gen.nov., represented by two new species, Khunnuchelys erinhotensis sp.nov. and Khunnuchelys kizylkumensis sp.nov. is described. Khunnuchelys erinhotensis is based on a large, well-preserved skull from the Iren Dabasu Formation in Inner Mongolia, and K. kizylkumensis is based on a series of partial skulls and isolated skull elements from the Dzhyrakuduk locality, Bissekty Formation, Uzbekistan. The occurrence of this trionychid in these two localities reinforces the suggestion of faunal similarity between the Iren Dabasu and Bissekty formations. Khunnuchelys is distinctive in the extensive development of the triturating surface, proportions of the skull, and features of the braincase. Conchochelys from the Paleocene of North America shares with Khunnuchelys derived features of the palate and braincase, and the two genera may be members of a monophyletic clade of trionychids. Autapomorphies of the triturating surface and associated features in Khunnuchelys are interpreted as durophagous specializations.
A juvenile specimen of Saurornithoides mongoliensis from the Upper Cretaceous of northern China
Authors: Currie Philip J. , Peng Jiang-Hua
Published: October 2010

A hind limb of Saurornithoides mongoliensis from the Djadokhta Formation equivalent beds (Upper Cretaceous) of Bayan Mandahu (People's Republic of China) provides more information on the anatomy of the leg of this species than any other known specimen. Although it shares apomorphies of all troodontid theropods, the metatarsus is relatively longer and more derived than that of Troodon itself. The specimen is of an immature individual, less than half the size of the holotype. The degree of ossification suggests that troodontids were well developed at birth and that parental care was probably unnecessary.
A new troodontid (Dinosauria, Theropoda) braincase from the Dinosaur Park Formation (Campanian) of Alberta
Authors: Currie Philip J. , Zhao Xi-Jin
Published: October 2010

A new, well-preserved specimen of Troodon formosus is the first to reveal the internal anatomy of the lower part of the braincase. In addition to providing new information on the brain of this highly encephalized dinosaur, the uncrushed bones clear up anatomical details left obscure by earlier studies. Computerized tomography (CT) scans reveal the nature of the inner ear and the course of the pneumatic ducts diverging from the middle ear. Evidence is presented to show that four of the five periotic pneumatic systems found in bird skulls are present in Troodon. The anterior tympanic recess is the most elaborate system, and diverticula from each side extend anteriorly, dorsally and, posteriorly from the middle ear. The posterior tympanic recess is located within the paroccipital process and the basioccipital, but the pneumatopore posterolateral to the stapedial recess is secondarily closed. The dorsal periotic sinus is represented by a smooth-surfaced concavity on the lateral surface of the prootic. The position of a pneumatic recess in this region is demonstrated by the presence of a pneumatopore in the quadrate. Diverticula from the anterior and posterior tympanic recesses are connected within braincase bones, and a possible pneumatopore in the prootic may connect these to the dorsal tympanic recess. The pneumatic condition of the troodontid articular is unknown. Contralateral connections of the sinus systems have been used to argue for a close relationship between birds and crocodiles, but their presence in this specimen suggests that they appeared more than once in archosaurs or that they are plesiomorphic for crocodiles, dinosaurs, and birds. Cranial pneumaticity cannot be used by itself to resolve the interrelationships of crocodiles, theropods, and birds, but other characters suggest derivation of birds from theropods.
A short history of research on
Archaeopteryx
and its relationship with dinosaurs
Authors: Wellnhofer Peter
Published: October 2010

Archaeopteryx
, first discovered in 1861 from the Solnhofen lithographic limestone of Bavaria, is the oldest feathered animal in the fossil record. Since its discovery it has been the focus of discussions about avian ancestry. Its mosaic of saurian and avian skeletal characters made it the classical ‘missing link’ of the Darwinian Theory of evolution. Even as early as 1868 Huxley advocated a close dinosaurian relationship of birds, a position followed later by such palaeontological luminaries as Marsh, Baur, Nopcsa and Abel, among others. Only in 1926, when Gerhard Heilmann published his seminal work,
The Origin of Birds
, was a ‘thecodontian’ origin of birds favoured. This book dominated perceptions of avian origins for the next half century, until John H. Ostrom reinvigorated the hypothesis of a dinosaurian ancestry for birds based on more
Archaeopteryx
specimens and new discoveries of theropod dinosaurs. Finally, the advent of cladistic methodology was instrumental in supporting
Archaeopteryx
and Aves within the theropod clade Maniraptora, a view almost ubiquituous today.
Thomas Henry Huxley and the reptile to bird transition
Authors: Switek Brian
Published: October 2010

The overwhelming evidence that birds evolved from maniraptoran theropod dinosaurs has rekindled an interest in the work of the Victorian anatomist Thomas Henry Huxley. Many popular and technical accounts credit Huxley with being the first to propose that birds evolved from dinosaurs, but this is a misinterpretation of Huxley's work. During the 1860s Huxley was preoccupied with identifying the basic ‘groundplans’ that united vertebrate forms. Birds and reptiles were two groups united by a shared body plan, with dinosaurs representing an intermediate form. Huxley did not begin to cast dinosaurs as transitional forms between birds and earlier reptiles until he read Ernst Haeckel's
Generelle Morphologie
, at which time Huxley amassed ample anatomical evidence to illustrate how birds could have evolved from something dinosaur-like. Even then, however, Huxley did not say that birds had evolved from dinosaurs. As he explicitly stated in public addresses during the 1870s, small bird-like dinosaurs like
Compsognathus
only represented the form of what the true ancestors of birds might have looked like. Bird-like dinosaurs chiefly served to show that such a transition was possible. Thus, Huxley's views on the evolution of birds were much more complex than many modern authors appreciate.
A history of digit identification in the manus of theropods (including Aves)
Authors: Hansen Kasper Lykke
Published: October 2010

The identification of avian and dinosaurian digits remains one of the major controversies in vertebrate evolution. A long history of morphological interpretations of fossil forms and studies of limb development in embryos has been given as evidence for two differing points of view. From an originally pentadactyl forelimb, either digits I, II and III form in the manus of birds and thus support a dinosaurian ancestry, or digits II, III and IV form in the manus supporting a more ancient ancestry or an evolutionary frame shift. A review of the history of research into the subject is presented here, dating from approximately 1825 to 2009.
Pteranodon
and beyond: the history of giant pterosaurs from 1870 onwards
Authors: Witton Mark P.
Published: October 2010

The immense size of many pterosaurs is now well known to academics and laymen alike, but truly enormous forms with wingspans more than twice those of the largest modern birds were not discovered until 83 years after the first pterosaur fossils were found. These remains were discovered in an expedition to the Cretaceous chalk deposits of Kansas led by O.C. Marsh in 1870: initially revealing animals with 6.6 m wingspans, Marsh eventually found material from animals estimated to span 7.6 m. Marsh's record breaking pterosaur – the largest flying animal known for nearly 80 years – was equalled by a supposed wing bone described by C.A.
Arambourg in 1954
, and then surpassed with the discovery of the 10 m span azhdarchid
Quetzalcoatlus northropi
by D. Lawson in 1972. Subsequent fragmentary azhdarchid discoveries suggest even larger forms: reinterpreting Arambourg's ‘wing bone’ as a cervical vertebra suggests an animal with an 11–13 m wingspan, while the Romanian taxon
Hatzegopteryx thambema
is a particularly large and robust form with a 12 m wingspan. Giant pterosaur footprints are also known, with the largest footprints recording walking azhdarchids of comparable size to those suggested by body fossils.
Sauropod dinosaur research: a historical review
Authors: Taylor Michael P.
Published: October 2010

In the 169 years since Owen named a tooth as
Cardiodon
, the study of sauropod dinosaurs has gone through several distinct periods. In the early years, a sequence of descriptions of isolated skeletal elements gave rise to a gradually emerging understanding of the animals that would later be known as sauropods. The second phase began in 1871 with Phillips's description of
Cetiosaurus oxoniensis
, the first reasonably complete sauropod, and continued with the Marsh-Cope Bone Wars and the description of the nearly complete sauropods
Camarasaurus
and ‘
Brontosaurus
’ (=
Apatosaurus
). As these and other genera became better known, a third phase began, exploring not just the remains but the lives of these giants, with arguments about posture and habitat to the fore, and with the public becoming increasingly aware of sauropods owing to skeletal mounts. A ‘dark age’ followed during and after World War II, with sauropods considered uninteresting evolutionary dead ends and largely ignored. This was brought to an end by the ‘dinosaur renaissance’ that began in the late 1960s, since when work has recommenced with new vigour, and the public has been introduced to a more vigorous and terrestrial image of sauropods through film and television. Both diversity and disparity of sauropods continue to increase through new descriptive work, and the group is now seen as more fascinating and worthy of study than ever before.
‘Old bones, dry subject’: the dinosaurs and pterosaur collected by Alfred Nicholson Leeds of Peterborough, England
Authors: Noè Leslie F. , Liston Jeff J. , Chapman Sandra D.
Published: October 2010

Alfred Nicholson Leeds, F.G.S., amassed one of the largest collections of fossil vertebrates from a single geological horizon anywhere in the world. The Leeds Collection is world famous for its large marine reptiles, but also includes the remains of a fine range of dinosaurs and a fragmentary pterosaur. The Leeds Collection ornithodirans were almost exclusively recovered from the Peterborough Member of the Oxford Clay Formation, with a single specimen of a sauropod derived from the underlying Kellaways Formation. The Leeds Collection includes the remains of at least 12 individual dinosaurs representing at least eight taxa (with other remains currently generically indeterminate) and a single fragmentary rhamphorhynchid pterosaur. Perhaps most intriguingly of all, in 1898 Alfred Leeds discovered a probable reptile egg, later attributed to a dinosaur. Each dinosaur and the pterosaur from the Leeds Collection is discussed, and, where known, details of the provenance, a brief history of research and pertinent archive material are included to provide the most comprehensive and up-to-date survey of the Leeds Collection ornithodirans to date.
Generalized impairment of vasodilator reactivity during hyperinsulinemia in patients with obesity-related metabolic syndrome
Authors: Schinzari Francesca , Tesauro Manfredi , Rovella Valentina , Galli Angelica , Mores Nadia , Porzio Ottavia , Lauro Davide , Cardillo Carmine
Published: October 2010

Defective insulin-dependent vasodilation might contribute importantly to metabolic and vascular abnormalities of the metabolic syndrome (MetS). However, despite extensive investigation, the precise mechanisms involved in insulin's vasoactive effects have not been fully elucidated. Therefore, this study sought to better characterize insulin's physiological actions on vascular reactivity and their potential derangement in the MetS. Forearm blood flow responses to graded doses of acetylcholine, sodium nitroprusside, and verapamil were assessed by strain-gauge plethysmography in patients with obesity-related MetS ( n = 20) and in matched controls ( n = 18) before and after intra-arterial infusion of insulin (0.2 mU·kg−1·min−1). Possible involvement of increased oxidative stress in the impaired insulin-stimulated vasodilator responsiveness of patients with MetS ( n = 12) was also investigated using vitamin C (25 mg/min). In control subjects, significant potentiation of the vasodilator responses to acetylcholine, nitroprusside, and verapamil was observed after insulin infusion (all P < 0.05). However, no significant change in vasodilator reactivity to either of these drugs was observed following hyperinsulinemia in patients with MetS (all P > 0.05). Interestingly, administration of vitamin C to patients with MetS during hyperinsulinemia significantly enhanced the vasodilator responsiveness to acetylcholine, nitroprusside, and verapamil (all P < 0.05 vs. hyperinsulinemia alone). In conclusion, insulin exerts a generalized facilitatory action on vasodilator reactivity, and this effect is impaired in patients with MetS likely because of increased oxidative stress. Given the importance of vasodilator reactivity in affecting glucose disposal and vascular homeostasis, this defect may then contribute to the development of metabolic and vascular complications in insulin-resistant states.
GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation
Authors: Maor Gila , Vasiliver-Shamis Gaia , Hazan-Brill Roni , Wertheimer Efrat , Karnieli Eddy
Published: October 2010

Skeletal growth, taking place in the cartilaginous growth plates of long bones, consumes high levels of glucose for both metabolic and anabolic purposes. We previously showed that Glut4 is present in growing bone and is decreased in diabetes. In the present study, we examined the hypothesis that in bone, GLUT4 gene expression and function are regulated via the IGF-I receptor (IGF-IR) and that Glut4 plays an important role in bone growth. Insulin and IGF-I actions on skeletal growth and glucose uptake were determined using mandibular condyle (MC) organ cultures and MC-derived primary cell cultures (MCDC). Chondrogenesis was determined by following proliferation and differentiation activities using immunohistochemical (IHC) analysis of proliferating cell nuclear antigen and type II collagen expression, respectively. Overall condylar growth was assessed morphometrically. GLUT4 mRNA and protein levels were determined using in situ hybridization and IHC, respectively. Glut4 translocation to the cell membrane was assessed using confocal microscopy analysis of GFP-Glut4 fusion-transfected cells and immunogold and electron microscopy on MC sections; glucose uptake was assayed by 2-deoxyglucose (2-DOG) uptake. Both IGF-I and insulin-stimulated glucose uptake in MCDC, with IGF-I being tenfold more potent than insulin. Blockage of IGF-IR abrogated both IGF-I- and insulin-induced chondrogenesis and glucose metabolism. IGF-I, but not insulin, induced Glut4 translocation to the plasma membrane. Additionally, insulin induced both GLUT4 and IGF-IR gene expression and improved condylar growth in insulin receptor knockout mice-derived MC. Moreover, silencing of GLUT4 gene in MCDC culture abolished both IGF-I-induced glucose uptake and chondrocytic proliferation and differentiation. In growing bone, the IGF-IR pathway stimulates Glut4 translocation and enhances glucose uptake. Moreover, intact Glut4 cellular levels and translocation machinery are essential for early skeletal growth.
Effect of the estrous cycle and surgical ovariectomy on energy balance, fuel utilization, and physical activity in lean and obese female rats
Authors: Giles Erin D. , Jackman Matthew R. , Johnson Ginger C. , Schedin Pepper J. , Houser Jordan L. , MacLean Paul S.
Published: October 2010

This study presents an in-depth analysis of the effects of obesity on energy balance (EB) and fuel utilization in adult female rats, over the estrous cycle and immediately after surgical ovariectomy (OVX), to model pre- and postmenopausal states, respectively. Female Wistar rats were fed a high-fat (46%) diet for 16 wk to produce mature lean and obese animals. Stage of estrous was identified by daily vaginal lavage, while energy intake (EI), total energy expenditure (TEE), and fuel utilization were monitored in a multichamber indirect calorimeter and activity was monitored by infrared beam breaks. Metabolic monitoring studies were repeated during the 3-wk period of rapid OVX-induced weight gain. Component analysis of TEE was performed to determine the nonresting and resting portions of energy expenditure. Obesity was associated with a greater fluctuation in EB across the estrous cycle. Cycling obese rats were less active, expended more energy per movement, and oxidized more carbohydrate than lean rats. The changes in EB over the cycle in lean and obese rats were driven by changes in EI. Finally, OVX induced a large positive energy imbalance in obese and lean rats. This resulted primarily from an increase in EI in both groups, with little change in TEE following OVX. These observations reveal a dominant effect of obesity on EB, fuel utilization, and activity levels in cycling rats, which has implications for studies focused on obesity and EB in female rodents.
Late-gestational systemic hypoxia leads to a similar early gene response in mouse placenta and developing brain
Authors: Trollmann Regina , Rehrauer Hubert , Schneider Christina , Krischke Gudrun , Huemmler Nicolas , Keller Stephan , Rascher Wolfgang , Gassmann Max
Published: October 2010

Late-gestational intrauterine hypoxia represents a well-known risk factor of acquired perinatal brain injury. Cell type and age-specific sensitivity of hypoxia-responsive genes to low-oxygen partial pressure is to be considered in the screening for early indicators of fetoplacental tissue hypoxia. To identify early hypoxia-induced alterations in gene expression during late-gestational hypoxia (6% O2, 6 h; gestational day 20) we compared primary mouse placenta and brain transcriptomes using high-density oligonucleotide microarrays. Upregulation of candidate marker genes for hypoxia was confirmed by quantitative RT-PCR and immunohistochemistry. Both developing brain and placenta were highly responsive to systemic hypoxia at the level of gene expression involving hypoxia-inducible transcription factor (HIF)-dependent genes and immediate early genes (IEG) (Fos, Jun, Egr1, Bhlhb2), apoptosis-promoting factors (Bnip3, Dusp1, Ier3) that were all upregulated, and genes modulating RNA binding and translation (Rbm3, Thap2, Lig4, Rbm12b) that mainly were downregulated. Functional activity of the HIF system was obvious from elevated expression of various known HIF target genes (Adm, Vegf, Hk2, Pdk1, Bnip3, Ier3, Dusp-1), indicating immediate availability among early response to acute hypoxia. In addition, genes not yet described as being hypoxia related were identified that are involved in angiogenesis/cell differentiation (Gna13, Gab2), mRNA processing, and embryonic development. RT-PCR of placenta and brain tissues confirmed upregulation of selected HIF target genes and IEG. These data indicate that the early hypoxia-induced genomic response of the placenta mirrors that of developing brain in a temporally parallel manner. Our observations implicate future diagnostic options to identify fetal and cerebral tissue hypoxia.
Topographic Organization of Excitatory and Inhibitory Commissural Connections in the Superior Colliculi and Their Functional Roles in Saccade Generation
Authors: Takahashi M. , Sugiuchi Y. , Shinoda Y.
Published: October 2010

Our electrophysiological study showed that there are topographic connections between excitatory and inhibitory commissural neurons (CNs) in one superior colliculus (SC) and tectoreticular neurons (TRNs) in the opposite SC. To obtain morphological evidence for these topographic commissural connections between the SCs, tracers were injected into various parts of the SC, the inhibitory burst neuron (IBN) area and Forel's field H (FFH), in the cat. Retrogradely labeled CNs were classified into three types according to their somatic areas and identified as GABA-positive or -negative immunohistochemically. Caudal SC injections labeled small GABA-positive CNs (<200 μm2) in the deep layers of the opposite rostral SC. Rostral SC injections mainly labeled medium-sized GABA-negative CNs (200–700 μm2) in the upper intermediate layer of the opposite rostral SC and small GABA-positive CNs in its deeper layers. Lateral SC injections labeled small GABA-positive CNs in the opposite medial SC and mainly medium-sized GABA-negative CNs in its lateral part. Medial SC injections labeled small GABA-positive CNs in the lateral SC and medium-sized GABA-negative CNs in the medial SC. In comparison, TRNs projecting to the FFH or IBN region were large (>700 μm2) and medium-sized. Many of the medium-sized GABA-negative CNs were TRNs projecting to the FFH. These results indicate that mirror-symmetric excitatory pathways link medial to medial (upper field) and lateral to lateral (lower field) parts of the SCs, whereas upper and lower field representations are linked by reciprocal inhibitory pathways in the tectal commissure. These connections presumably play important roles in conjugate upward and downward vertical saccades.
AVR/NAVR deficiency lowers blood pressure and differentially affects urinary concentrating ability, cognition, and anxiety-like behavior in male and female mice
Authors: Herrera Victoria L. M. , Bagamasbad Pia , Decano Julius L. , Ruiz-Opazo Nelson
Published: October 2010

Arginine vasopressin (AVP) and angiotensin II (ANG II) are distinct peptide hormones involved in multiple organs modulating renal, cardiovascular, and brain functions. They achieve these functions via specific G protein-coupled receptors, respectively. The AVR/NAVR locus encodes two overlapping V2-type vasopressin isoreceptors: angiotensin-vasopressin receptor (AVR) responding to ANG II and AVP equivalently, and nonangiotensin vasopressin receptor (NAVR), which binds vasopressin exclusively. AVR and NAVR are expressed from a single gene by alternative promoter usage that is synergistically upregulated by testosterone and estrogen. This study tested the hypothesis that AVR/NAVR modulates urinary concentrating ability, blood pressure, and cognitive performance in vivo in a sex-specific manner. We developed a C57BL/6 inbred AVR/NAVR−/− knockout mouse that showed lower blood pressure in both male and female subjects and a urinary-concentrating defect restricted to male mice. We also detected sex-specific effects on cognitive and anxiety-like behaviors. AVR/NAVR−/− male mice exhibited impaired visuospatial and associative learning, while female mice showed improved performance in both type of cognition. AVR/NAVR deficiency produced an anxiolytic-like effect in female mice, while males were unaffected. Analysis of AVR- and NAVR-mediated phosphorylation/dephosphorylation of signaling proteins revealed activation/deactivation of known modulators of cognitive function. Our studies identify AVR/NAVR as key receptors involved in blood pressure regulation and sex-specific modulation of renal water homeostasis, cognitive function, and anxiety-like behavior. As such, the AVR/NAVR receptor system provides a molecular mechanism for sexually diergic traits and a putative common pathway for the emerging association of hypertension and cognitive decline and dementia.
Identification of Predictive Markers of Response to the MEK1/2 Inhibitor Selumetinib (AZD6244) in K-ras–Mutated Colorectal Cancer
Authors: Tentler John J. , Nallapareddy Sujatha , Tan Aik Choon , Spreafico Anna , Pitts Todd M. , Morelli M. Pia , Selby Heather M. , Kachaeva Maria I. , Flanigan Sara A. , Kulikowski Gillian N. , Leong Stephen , Arcaroli John J. , Messersmith Wells A. , Eckhardt S. Gail
Published: October 2010

Mutant K-ras activity leads to the activation of the RAS/RAF/MEK/ERK pathway in approximately 44% of colorectal cancer (CRC) tumors. Accordingly, several inhibitors of the MEK pathway are under clinical evaluation in several malignancies including CRC. The aim of this study was to develop and characterize predictive biomarkers of response to the MEK1/2 inhibitor AZD6244 in CRC in order to maximize the clinical utility of this agent. Twenty-seven human CRC cell lines were exposed to AZD6244 and classified according to the IC50 value as sensitive (≤0.1 μmol/L) or resistant (>1 μmol/L). All cell lines were subjected to immunoblotting for effector proteins, K-ras/BRAF mutation status, and baseline gene array analysis. Further testing was done in cell line xenografts and K-ras mutant CRC human explants models to develop a predictive genomic classifier for AZD6244. The most sensitive and resistant cell lines were subjected to differential gene array and pathway analyses. Members of the Wnt signaling pathway were highly overexpressed in cell lines resistant to AZD6244 and seem to be functionally involved in mediating resistance by shRNA knockdown studies. Baseline gene array data from CRC cell lines and xenografts were used to develop a k-top scoring pair (k-TSP) classifier, which predicted with 71% accuracy which of a test set of patient-derived K-ras mutant CRC explants would respond to AZD6244, providing the basis for a patient-selective clinical trial. These results also indicate that resistance to AZD6244 may be mediated, in part, by the upregulation of the Wnt pathway, suggesting potential rational combination partners for AZD6244 in CRC. Mol Cancer Ther; 9(12); 3351–62. ©2010 AACR.
Behavior of Ebstein’s Anomaly: Single-Center Experience and Midterm Follow-Up
Authors: Legius Barbara , Van De Bruaene Alexander , Van Deyk Kristien , Gewillig Marc , Troost Els , Meyns Bart , Budts Werner
Published: October 2010

Objectives: Ebstein’s anomaly, characterized by an apical displacement of the tricuspid valve into the right ventricle, occurs in approximately 1/200,000 live births. Because long-term follow-up data of adults with Ebstein’s anomaly are scarce, we evaluated the outcome of our Ebstein’s anomaly patients. Methods: All patients >16 years and registered in the congenital heart disease database of our hospital with isolated Ebstein’s anomaly were selected for the study. Records were reviewed for outcome. Results: Forty-nine patients (21 males, mean age at diagnosis 29.1 ± 20.7 years) were followed for a mean time of 11.4 years (range 1.1–32.4). Twenty-five patients (51%) underwent tricuspid valve surgery (16 valvuloplasty and 9 valve replacement). Eight patients (32%) required redo tricuspid valve surgery. Twenty-six patients (52.1%) exhibited supraventricular arrhythmia, and the typical Wolff-Parkinson-White syndrome occurred in 15 patients (31.2%). Seventeen patients (34.7%) underwent ablation therapy and 5 patients (10.4%) required pacemaker implantation. Conclusions: Half of the patients with Ebstein’s anomaly needed tricuspid valve surgery and redo surgery was not uncommon. Supraventricular arrhythmia occurred frequently and ablation therapy was often indicated. Careful follow-up is obligate, as some complications occur for the first time in adulthood.
Cytochrome P450 2C19 Polymorphism, Suboptimal Reperfusion and All-Cause Mortality in Patients with Acute Myocardial Infarction
Authors: Małek Łukasz A. , Przyłuski Jakub , Śpiewak Mateusz , Kłopotowski Mariusz , Kostrzewa Grażyna , Kruk Mariusz , Płoski Rafał , Witkowski Adam , Rużyłło Witold
Published: October 2010

Objectives: To determine whether the 681 G>A (*2) polymorphism of cytochrome P450 (CYP2C19) is related to suboptimal reperfusion and mortality in patients with acute myocardial infarction (AMI) pretreated with clopidogrel. Methods: Thestudy included 276 consecutive patients with AMI in whom percutaneous coronary intervention (PCI) with stenting was attempted. Four-year follow-up for all-cause mortality was obtained. Results: There were 15 failed procedures (5.4%). In the remaining 261 patients, suboptimal reperfusion (post-PCI TIMI flow <3) was observed in 12.6% of the cases. There were 56 carriers (50 heterozygous and 6 homozygous) of CYP2C19*2. The prevalence of carriers in patients with suboptimal flow was 39.4% in comparison to 18.9% in the other patients (p = 0.01). Independent predictors of suboptimal reperfusion were initial TIMI flow ≤1 (OR = 5.9, 95% CI 2.2–16.2, p = 0.001) and CYP2C19*2 (OR = 2.9, 95% CI 1.3–6.6, p = 0.01). Thirty patients died during follow-up (11.5%). Four-year mortality tended to be higher in carriers of CYP2C19*2 (17.9%) versus non-carriers (9.8%; p = 0.09), but the only independent predictors of death were age (HR = 2.0, 95% CI = 1.4–2.8, p = 0.0001) and suboptimal reperfusion (HR = 3.6, 95% CI 1.5–8.8, p = 0.004). Conclusions: The CYP2C19*2 allele is an independent predictor of suboptimal reperfusion in patients with AMI undergoing PCI with stenting after pretreatment with clopidogrel and may increase the risk of all-cause mortality.
Conversion of Darbepoetin to Low Doses of CERA Maintains Hemoglobin Levels in Non-Dialysis Chronic Kidney Disease Patients
Authors: Minutolo Roberto , Zamboli Pasquale , Chiodini Paolo , Mascia Sara , Vitiello Santo , Stanzione Giovanna , Bertino Valerio , Conte Giuseppe , De Nicola Luca
Published: October 2010

Background/Aims: Finding the lowest effective dose of erythropoietin-stimulating agents is critical in the management of renal anemia. We evaluated the efficacy of converting darbepoetin to CERA at doses lower than those usually recommended. Methods: We selected consecutive non-dialysis chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week in absence of iron deficiency, recent blood transfusion, bleeding, neoplasia, myocardial infarction/stroke in the last 3 months. Darbepoetin ≤20 µg/week was shifted to CERA 75 µg/month, while darbepoetin 21–40 µg/week to CERA 100 µg/month. Primary endpoint was the change in hemoglobin (Hb goal, 11–13 g/dl) at month 3, 6, 9 and 12. Results: Studied patients (n = 37) were aged 70 ± 13 years and GFR was 30 ± 12 ml/min/1.73 m2; prevalence of males, diabetes and prior cardiovascular disease was 43, 45 and 40%, respectively. Before switching, efficacy population received darbepoetin 18 ± 10 µg/week with 28 patients receiving ≤20 µg/week. Prevalence of Hb goal at baseline was 75.7% and did not change at months 3 (70.3%), 6 (70.3%), 9 (72.2%), and 12 (80.0%). CERA dose remained unchanged during the study (81 ± 11, 82 ± 16, 91 ± 30, 90 ± 54 and 88 ± 61 µg/month). Out of the 438 visits performed, CERA dose was increased in 52 (11.9%) and reduced in 36 (8.2%) visits. Blood pressure, Hb, GFR, transferrin saturation and ferritin did not change. Conclusions: In chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week, CERA can be efficaciously used at doses lower than those recommended.
Streptomyces coelicolor A3(2) Produces a New Yellow Pigment Associated with the Polyketide Synthase Cpk
Authors: Pawlik Krzysztof , Kotowska Magdalena , Kolesiński Piotr
Published: October 2010

Streptomyces coelicolor A3(2) is an extensively studied model organism for the genetic studies of Streptomycetes – a genus known for the production of a vast number of bioactive compounds and complex regulatory networks controlling morphological differentiation and secondary metabolites production. We present the discovery of a presumptive product of the Cpk polyketide synthase. We have found that on the rich medium without glucose S. coelicolor A3(2) produces a yellow compound secreted into the medium. We have proved by complementation that production of the observed yellow pigment is dependent on cpk gene cluster previously described as cryptic type I polyketide synthase cluster. The pigment production depends on the medium composition, does not occur in the presence of glucose, and requires high density of spore suspension used for inoculation.
Development and Validation of Risk Adjustment Models for Long-Term Mortality and Myocardial Infarction Following Percutaneous Coronary Interventions
Authors: Singh Mandeep , Holmes David R. , Lennon Ryan J. , Rihal Charanjit S.
Published: October 2010

Background—

Existing models for outcome after percutaneous coronary interventions (PCIs) lack assessment of long-term prognosis. Our goal was to derive 1- and 5-year mortality and mortality/myocardial infarction (MI) risk models for PCI outcomes from simple, easily obtainable clinical and laboratory variables.

Methods and Results—

Using the Mayo Clinic registry, we analyzed long-term mortality and mortality/MI following PCIs on 9165 unique patients from January 1, 2001, through December 31, 2007. Cox proportional hazards regression was used to model the calculated risk score and major procedural complications. A total of 1243 patients died, and 696 had MI. Separate risk models derived from clinical, procedural, and laboratory characteristics were made for mortality and mortality/MI. Older age, comorbid conditions, low ejection fraction, acute MI, history of smoking, heart failure, hyperlipidemia, 3-vessel disease, procedural failure, ventricular arrhythmia during PCI, and low medication score were predictors of long-term mortality and mortality/MI. Simple integer scores stratified patients into low, moderate, high, and very high risk for subsequent events. Models had adequate goodness of fit, and areas under the receiver operating characteristic curve were 0.786 and 0.728 for mortality and mortality/MI, respectively, indicating good overall discrimination. Bootstrap analysis indicated that the model was not overfit to the available data set.

Conclusions—

Easily obtainable variables can be combined into a convenient risk scoring system at the time of patient dismissal following PCI to accurately predict long-term mortality and mortality/MI. This model may be useful for providing patients with individualized, evidence-based estimates of long-term risk.
Prognostic Value of Isolated Troponin I Elevation After Percutaneous Coronary Intervention
Authors: Cavallini Claudio , Verdecchia Paolo , Savonitto Stefano , Arraiz Gustavo , Violini Roberto , Olivari Zoran , Rubartelli Paolo , De Servi Stefano , Plebani Mario , Steffenino Giuseppe , Sbarzaglia Paolo , Ardissino Diego ,   on behalf of the Italian “Atherosclerosis, Thrombosis and Vascular Biology” and “Society for Invasive Cardiology–GISE” Investigators
Published: October 2010

Background—

Mild elevations of cardiac troponin are frequent after percutaneous coronary intervention (PCI). Their prognostic value is uncertain in the absence of changes in creatine kinase-MB (CK-MB).

Methods and Results—

We evaluated the relation between isolated elevations of cardiac troponin I (cTnI) and all-cause mortality. We studied 3494 consecutive patients who underwent PCI in 16 Italian tertiary cardiology centers. CK-MB and cTnI were analyzed in a central laboratory. Duration of follow-up was 2 years. The present analysis was restricted to 2362 patients with normal CK-MB and cTnI values at baseline and no CK-MB elevation after PCI. A rise in cTnI after PCI >0.15 ng/mL, the upper reference limit, was found in 932 patients (39.4%). A rise >0.45 ng/mL (>3×upper reference limit) was found in 467 patients (19.7%). Compared with patients with normal cTnI, those with cTnI elevation >0.15 ng/mL showed a slightly increased mortality (3.8% versus 2.6%; hazard ratio, 1.53; 95% confidence interval, 0.97 to 2.42;
P
=0.069). A cTnI elevation >0.45 ng/mL was associated with a higher risk of mortality (4.5% versus 2.7%; hazard ratio, 1.68; 95% confidence interval, 1.01 to 2.80;
P
=0.044), which, however, did not remain significant after adjustment for concomitant risk factors (hazard ratio, 1.45; 95% confidence interval, 0.86 to 2.46;
P
=0.162). Postprocedural cTnI elevation was associated with coronary and clinical features consistent with a worse risk profile.

Conclusions—

In the absence of a rise in CK-MB, elevated cTnI levels after PCI are associated with a modest increased risk of death. However, this is not independent of the concomitant adverse baseline clinical characteristics of these patients.
Utilization of Secondary Prevention Therapies in Patients With Nonobstructive Coronary Artery Disease Identified During Cardiac Catheterization
Authors: Maddox Thomas M. , Ho P. Michael , Roe Matthew , Dai David , Tsai Thomas T. , Rumsfeld John S.
Published: October 2010

Background—

Secondary prevention therapies are indicated for patients with coronary artery disease (CAD). However, patients with nonobstructive CAD may be less likely to receive these therapies compared with patients with obstructive CAD. Therefore, we compared rates of secondary prevention medication prescription between patients with nonobstructive and obstructive CAD.

Methods and Results—

We conducted a retrospective cohort study of 1 489 745 CAD patients undergoing cardiac catheterization in 786 US centers between 2004 and 2007. We measured rates of aspirin, statin, β-blocker, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) prescription at hospital discharge among eligible patients; 237 167 (15.9%) patients had nonobstructive CAD and 1 252 578 (84.1%) had obstructive CAD. Compared with obstructive CAD patients, nonobstructive CAD patients had significantly lower rates of rates of aspirin (72.7% versus 90.9%), statin (60.0% versus 80.3%), β-blocker (57.9% versus 79.4%), and ACEI/ARB (45.9% versus 58.6%; all probability values <0.0001) prescription at hospital discharge. After multivariable adjustment, nonobstructive CAD patients remained significantly less likely to receive prescriptions for aspirin (odds ratio, 0.37; 95% confidence interval, 0.35 to 0.39), statins (odds ratio, 0.45; 95% confidence interval, 0.43 to 0.48), β-blockers (odds ratio, 0.46; 95% CI, 0.44 to 0.47), or ACEI/ARBs (odds ratio, 0.83; 95% confidence interval, 0.8 to 0.86) compared with obstructive CAD patients. Secondary analyses of selected subgroups supported the primary findings.

Conclusions—

Patients with nonobstructive CAD were significantly less likely to receive secondary prevention medication prescription at hospital discharge, as compared with patients with obstructive CAD. These findings highlight an opportunity to improve the quality of care for CAD patients with nonobstructive disease.
The Impact of Hospital Cardiac Specialization on Outcomes After Coronary Artery Bypass Graft Surgery
Authors: Girotra Saket , Lu Xin , Popescu Ioana , Vaughan-Sarrazin Mary , Horwitz Phillip A. , Cram Peter
Published: October 2010

Background—

Hospital volume has been widely embraced as a proxy measure for hospital quality; little attention has been focused on an alternative quality measure–hospital specialization. Even though specialization occurs on a continuum, previous studies have only focused on a small number of highly specialized hospitals (single-specialty hospitals). Studies on the broad relationship between hospital specialization and outcomes after coronary artery bypass grafting (CABG) are limited.

Methods and Results—

We conducted a retrospective cohort study of 705 084 Medicare patients (1130 hospitals) who underwent CABG during 2001 to 2005. We stratified hospitals into quintiles, based on their degree of cardiac specialization (proportion of a hospital's Medicare discharges classified as Major Diagnostic Category 5–cardiovascular diseases). We compared patient and hospital characteristics and outcomes across quintiles of cardiac specialization. Patient characteristics were generally similar across quintiles, but mean annual CABG volume increased progressively from quintile 1 (least specialized) to quintile 5 (most specialized). Unadjusted 30-day mortality was similar at hospitals in quintiles 1 to 4 (4.8%), except quintile 5, where mortality was lower (4.3%). A strong inverse association was seen between hospital cardiac specialization and 30-day mortality after adjustment for patient characteristics (
P
trend
=0.001). However, this was no longer significant after additional adjustment for CABG volume (
P
trend
=0.65). Results were similar for other mortality outcomes and length of stay.

Conclusions—

After accounting for patient characteristics and CABG volume, greater cardiac specialization was not associated with clinically significant improvement in patient outcomes. This study calls into question the benefit of cardiac specialization for the vast majority of CABG-performing US hospitals.