bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Adnectin CT-322 is a novel VEGF receptor 2 inhibitor that decreases tumor burden in an orthotopic mouse model of pancreatic cancer
Authors: Dineen Sean P , Sullivan Laura A , Beck Adam W , Miller Andrew F , Carbon Juliet G , Mamluk Roni , Wong Henry , Brekken Rolf A 
Published: November 2008

Abstract

Background
Pancreatic cancer continues to have a 5-year survival of less than 5%. Therefore, more effective therapies are necessary to improve prognosis in this disease. Angiogenesis is required for tumor growth, and subsequently, mediators of angiogenesis are attractive targets for therapy. Vascular endothelial growth factor (VEGF) is a well-characterized mediator of tumor angiogenesis that functions primarily by binding and activating VEGF receptor 2 (VEGFR2). In this study, we evaluate the use of CT-322, a novel biologic (Adnectin). This small protein is based on a human fibronectin domain and has beneficial properties in that it is fully human, stable, and is produced in bacteria. CT-322 binds to and inhibits activation of VEGFR2.

Methods
The efficacy of CT-322 was evaluated in vivo using two orthotopic pancreatic tumor models. The first model was a human tumor xenograft where MiaPaCa-2 cells were injected into the tail of the pancreas of nude mice. The second model was a syngeneic tumor using Pan02 cells injected into pancreas of C57BL/6J mice. In both models, therapy was initiated once primary tumors were established. Mice bearing MiaPaCa-2 tumors were treated with vehicle or CT-322 alone. Gemcitabine alone or in combination with CT-322 was added to the treatment regimen of mice bearing Pan02 tumors. Therapy was given twice a week for six weeks, after which the animals were sacrificed and evaluated (grossly and histologically) for primary and metastatic tumor burden. Primary tumors were also evaluated by immunohistochemistry for the level of apoptosis (TUNEL), microvessel density (MECA-32), and VEGF-activated blood vessels (Gv39M).

Results
Treatment with CT-322 was effective at preventing pancreatic tumor growth and metastasis in orthotopic xenograft and syngeneic models of pancreatic cancer. Additionally, CT-322 treatment increased apoptosis, reduced microvessel density and reduced the number of VEGF-activated blood vessels in tumors. Finally, CT-322, in combination with gemcitabine was safe and effective at controlling the growth of syngeneic pancreatic tumors in immunocompetent mice.

Conclusion
We conclude that CT-322 is an effective anti-VEGFR2 agent and that further investigation of CT-322 for the treatment of pancreatic cancer is warranted.
Derivation and internal validation of an equation for albumin-adjusted calcium
Authors: James Matthew T , Zhang Jianguo , Lyon Andrew W , Hemmelgarn Brenda R 
Published: November 2008

Abstract

Background
Previously published equations to adjust calcium for albumin concentration may vary depending on factors such as the type of reagents used. Albumin-adjusted calcium equations derived from laboratories using the bromocresol purple (BCP) albumin binding reagent have not been described.

Methods
The linear regression equation for the binding of calcium and BCP-albumin was derived in a cohort of 4613 outpatients, and the albumin-adjusted calcium equation was internally validated in a separate cohort of 1538 subjects. The performance of this equation was compared with a previously published equation (adjusted [Ca](mmol/L) = total [Ca](mmol/L) + 0.02 (40 - [albumin] (g/L)) in 343 subjects with albumin < 33 g/L (below reference range).

Results
The local adjustment equation was expressed by the relationship; adjusted [Ca](mmol/L) = total [Ca](mmol/L) + 0.012 (39.9 - [albumin](g/L)). The equation showed evidence of good internal validity (shrinkage value of adjusted r2 = -0.0059). Classification of calcium status differed between the two equations in 47 of 343 subjects with low serum albumin (weighted κ = 0.46; moderate agreement).

Conclusion
A locally derived and internally validated albumin-adjusted calcium equation differed from previously published equations and resulted in important differences in classification of calcium status in hypoalbuminemia patients. Individual laboratories should determine their own linear regression equation for calcium on albumin rather than relying on published formulas.
Pyrethroid resistance in the major malaria vector Anopheles arabiensis from Gwave, a malaria-endemic area in Zimbabwe
Authors: Munhenga Givemore , Masendu Hieronymo T , Brooke Basil D , Hunt Richard H , Koekemoer Lizette K 
Published: November 2008

Abstract

Background
Insecticide resistance can present a major obstacle to malaria control programmes. Following the recent detection of DDT resistance in Anopheles arabiensis in Gokwe, Zimbabwe, the underlying resistance mechanisms in this population were studied.

Methods
Standard WHO bioassays, using 0.75% permethrin, 4% DDT, 5% malathion, 0.1% bendiocarb and 4% dieldrin were performed on wild-collected adult anopheline mosquitoes and F1 progeny of An. arabiensis reared from wild-caught females. Molecular techniques were used for species identification as well as to identify knockdown resistance (kdr) and ace-1 mutations in individual mosquitoes. Biochemical assays were used to determine the relative levels of detoxifying enzyme systems including non-specific esterases, monooxygenases and glutathione-S-transferases as well as to detect the presence of an altered acetylcholine esterase (AChE).

Results

Anopheles arabiensis was the predominant member of the Anopheles gambiae complex. Of the 436 An. arabiensis females, 0.5% were positive for Plasmodium falciparum infection. WHO diagnostic tests on wild populations showed resistance to the pyrethroid insecticide permethrin at a mean mortality of 47% during February 2006 and a mean mortality of 68.2% in January 2008. DDT resistance (68.4% mean mortality) was present in February 2006; however, two years later the mean mortality was 96%. Insecticide susceptibility tests on F1
An. arabiensis families reared from material from two separate collections showed an average mean mortality of 87% (n = 758) after exposure to 4% DDT and 65% (n = 587) after exposure to 0.75% permethrin. Eight families were resistant to both DDT and permethrin. Biochemical analysis of F1 families reared from collections done in 2006 revealed high activity levels of monooxygenase (48.5% of families tested, n = 33, p < 0.05), glutathione S-transferase (25.8% of families tested, n = 31, p < 0.05) and general esterase activity compared to a reference susceptible An. arabiensis colony. Knockdown resistance (kdr) and ace-I

R
mutations were not detected.

Conclusion
This study confirmed the presence of permethrin resistance in An. arabiensis populations from Gwave and emphasizes the importance of periodic and ongoing insecticide susceptibility testing of malaria vector populations whose responses to insecticide exposure may undergo rapid change over time.
Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation
Authors: Briggs Andrew , Wild Diane , Lees Michael , Reaney Matthew , Dursun Serdar , Parry David , Mukherjee Jayanti 
Published: November 2008

Abstract

Objective
To examine the impact of schizophrenia, its treatment and treatment-related adverse events related to antipsychotics, on quality of life from the perspective of schizophrenia patients and laypersons.

Methods
Health state descriptions for stable schizophrenia, extra pyramidal symptoms (EPS), hyperprolactinemia, diabetes, weight gain and relapse were developed based on a review of the literature and expert opinion. The quality of life impact of each health state was elicited using a time trade-off instrument administered by interview to 49 stable schizophrenia patients and 75 laypersons. Regression techniques were employed to examine the importance of subject characteristics on health-related utility scores.

Results
Patients and laypersons completed the interview in similar times. Stable schizophrenia had the highest mean utility (0.87 and 0.92 for laypersons and patients respectively), while relapse (0.48 and 0.60) had the lowest mean utility. Of the treatment-related adverse events, EPS had the lowest mean utility (0.57 and 0.72, respectively). Age, gender and PANSS score did not influence the utility results independently of health state. On average, patient utilities are 0.077 points higher than utilities derived from laypersons, although the ranking was similar between the two groups.

Conclusion
Events associated with schizophrenia and treatment of schizophrenia can bring about a significant detriment in patient quality of life, with relapse having the largest negative impact. Results indicate that patients with stable schizophrenia are less willing to trade years of life to avoid schizophrenia-related symptoms compared to laypersons. Both sets of respondents showed equal ability to complete the questionnaire.
Forelimb proportions and kinematics: how are small primates different from other small mammals?
Authors: Schmidt Manuela 
Published: November 2008

SUMMARYThe crouched limb posture of small mammals enables them to react to unexpected irregularities in the support. Small arboreal primates would benefit from these kinematics in their arboreal habitat but it has been demonstrated that primates display certain differences in forelimb kinematics to other mammals. The objective of this paper is to find out whether these changes in forelimb kinematics are related to changes in body size and limb proportions. As primates descended from small ancestors, a comparison between living small primates and other small mammals makes it possible to determine the polarity of character transformations for kinematic and morphometric features proposed to be unique to primates. Walking kinematics of mouse lemurs, brown lemurs, cotton-top tamarins and squirrel monkeys was investigated using cineradiography. Morphometry was conducted on a sample of 110 mammals comprising of primates, marsupials, rodents and carnivores. It has been shown that forelimb kinematics change with increasing body size in such a way that limb protraction increases but retraction decreases. Total forelimb excursion, therefore, is almost independent of body size. Kinematic changes are linked to changes in forelimb proportions towards greater asymmetry between scapula and radius. Due to the spatial restriction inherent in the diagonal footfall sequence of primates, forelimb excursion is influenced by the excursion of the elongated hind limb. Hindlimb geometry, however, is highly conserved, as has been previously shown. The initial changes in forelimb kinematics might, therefore, be explained as solutions to a constraint rather than as adaptations to the particular demands of arboreal locomotion.
Ontogenetic changes in photoreceptor opsin gene expression in coho salmon(Oncorhynchus kisutch, Walbaum)
Authors: Temple S. E. , Veldhoen K. M. , Phelan J. T. , Veldhoen N. J. , Hawryshyn C. W. 
Published: November 2008

SUMMARYPacific salmonids start life in fresh water then migrate to the sea, after a metamorphic event called smoltification, later returning to their natal freshwater streams to spawn and die. To accommodate changes in visual environments throughout life history, salmon may adjust their spectral sensitivity. We investigated this possibility by examining ontogenetic and thyroid hormone (TH)-induced changes in visual pigments in coho salmon(Oncorhynchus kisutch, Walbaum). Using microspectrophotometry, we measured the spectral absorbance (quantified by λmax) of rods, and middle and long wavelength-sensitive (MWS and LWS) cones in three age classes of coho, representing both freshwater and marine phases. Theλ max of MWS and LWS cones differed among freshwater (alevin and parr) and ocean (smolt) phases. The λmax of rods, on the other hand, did not vary, which is evidence that vitamin A1/A2 visual pigment chromophore ratios were similar among freshwater and ocean phases when sampled at the same time of year. Exogenous TH treatment long wavelength shifted the λmax of rods, consistent with an increase in A2. However, shifts in cones were greater than predicted for a change in chromophore ratio. Real-time quantitative RT-PCR demonstrated that at least two RH2 opsin subtypes were expressed in MWS cones, and these were differentially expressed among alevin,parr and TH-treated alevin groups. Combined with changes in A1/A2 ratio, differential expression of opsin subtypes allows coho to alter the spectral absorbance of their MWS and LWS cones by as much as 60 and 90 nm, respectively. To our knowledge, this is the largest spectral shift reported in a vertebrate photoreceptor.
Stabilization and mobility of the head, neck and trunk in horses during overground locomotion: comparisons with humans and other primates
Authors: Dunbar Donald C. , Macpherson Jane M. , Simmons Roger W. , Zarcades Athina 
Published: November 2008

SUMMARYSegmental kinematics were investigated in horses during overground locomotion and compared with published reports on humans and other primates to determine the impact of a large neck on rotational mobility (&gt;20 deg.) and stability (≤20 deg.) of the head and trunk. Three adult horses (Equus caballus) performing walks, trots and canters were videotaped in lateral view. Data analysis included locomotor velocity, segmental positions, pitch and linear displacements and velocities, and head displacement frequencies. Equine, human and monkey skulls and cervical spines were measured to estimate eye and vestibular arc length during head pitch displacements. Horses stabilized all three segments in all planes during all three gaits, unlike monkeys and humans who make large head pitch and yaw rotations during walks,and monkeys that make large trunk pitch rotations during gallops. Equine head angular displacements and velocities, with some exceptions during walks, were smaller than in humans and other primates. Nevertheless, owing to greater off-axis distances, orbital and vestibular arc lengths remained larger in horses, with the exception of head–neck axial pitch during trots, in which equine arc lengths were smaller than in running humans. Unlike monkeys and humans, equine head peak-frequency ranges fell within the estimated range in which inertia has a compensatory stabilizing effect. This inertial effect was typically over-ridden, however, by muscular or ligamentous intervention. Thus, equine head pitch was not consistently compensatory, as reported in humans. The equine neck isolated the head from the trunk enabling both segments to provide a spatial reference frame.
The functional significance of the lower temporal bar inSphenodon punctatus
Authors: Schaerlaeken Vicky , Herrel Anthony , Aerts Peter , Ross Callum F. 
Published: November 2008

SUMMARYOne of the major conundrums in the evolution of vertebrate cranial design is the early loss and frequent redevelopment of the lower temporal bar in diapsids. Whereas it has been proposed that the reduction of the lower temporal bar allows for an increase in jaw adductor mass and bite force, this has never been tested experimentally. As the sole recent representative of the Rhynchocephalia, Sphenodon punctatus is different from other extant lepidosaurians in having a fully diapsid skull and in using translation to shear food rather than using the typical puncture-crushing of other lizards. In the present study, we show that S. punctatus has lower bite forces compared with extant lepidosaurians. Moreover, dissection of the jaw muscles of an adult S. punctatus shows that the mass of the external jaw adductor muscle is significantly smaller than that of lizards, probably accounting for the lower measured bite forces. An analysis of the transport cycles suggests a less efficient prey transport in S. punctatuscompared with an agamid lizard of similar size in terms of handling time and number of cycles needed to crush similar prey. Modelling of biting in S. punctatus suggests a different role of the jaw adductor muscles during biting and a clear functional role for the lower temporal bar. Future finite element models may provide better insights into the function of the lower temporal bar in S. punctatus.
Timing of the daily temperature cycle affects the critical arousal temperature and energy expenditure of lesser long-eared bats
Authors: Turbill Christopher , Körtner Gerhard , Geiser Fritz 
Published: November 2008

SUMMARYDaily patterns of body temperature (Tb) and energy expenditure in heterothermic endotherms are affected by changes in ambient temperature (Ta) and selection of suitable microclimates,yet most laboratory studies employ constant Ta to measure metabolic rates. In particular, exposure to a daily temperature cycle, even within rest shelters, may be important in timing of torpor and arousal and determining resting energy costs in wild animals. We tested how captive bats(Nyctophilus geoffroyi; 7 g) exposed to a diurnal Ta fluctuation (between 13°C and 27°C), similar to natural conditions in their summer tree roosts, adjusted the timing of daily arousals. To distinguish the effects of Ta and passive rewarming from time of the day, we shifted the heating phase to commence at 06:00 h, 09:00 h or 12:00 h on each day. Bats entered torpor overnight and aroused the next day at a time corresponding to rising Taand passive rewarming. The critical Ta (and torpid Tb) for arousal was not fixed, however, but was lower when heating occurred later in the rest phase, providing the first evidence that the critical arousal Ta is affected by time of the day. Bats re-entered torpor in response to cooling late in the afternoon, yet always aroused at lights off. A period of normothermic thermoregulation was therefore closely synchronised with maximum daily Ta,indicating a trade-off between the benefits and energetic costs of normothermia during resting. Our experiment clearly shows that a daily Ta cycle affects the thermoregulatory behaviour and energetics of these small bats. More generally, these results demonstrate the critical influence of behavioural decisions on the daily energy expenditure of small heterothermic mammals.
Switching to fast growth: the insulin-like growth factor (IGF) system in skeletal muscle of Atlantic salmon
Authors: Bower Neil I. , Li Xuejun , Taylor Richard , Johnston Ian A. 
Published: November 2008

SUMMARY
In this study we describe the complete coding sequence for insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), insulin-like growth factor binding protein (IGFBP) 1, 2, 4, 5 and 6 and IGFBP-related protein 1 (IGFBP-rP1) of Atlantic salmon (Salmo salar L.). We also report the characterisation of two gene paralogues of IGFBP-2 and IGFBP-5. Following 22 days restricted feeding (0 d) to achieve zero growth, fish were fed to satiation and sampled at 3, 5, 7, 14, 30 and 60 days. Expression profiles for genes involved in the IGF signalling pathway in fast myotomal muscle were determined using real-time quantitative RT-PCR. The transition from zero to fast growth is characterised by constitutive upregulation of IGF-I and IGFBP-4, a transient increase in IGFBP-5.2, and downregulation of IGFBP-2.1, IGF-II, IGF2R (IGF-II receptor) and IGFR1a (IGF-I receptor a). Expression of IGFBP-2.2, IGFBP-5.1, IGFBP-6, IGFBP-rP1 and IGFR1b showed little or no response to feeding. Expression of the myogenic marker genes myogenin, MHC and MLC2 were higher with feed restriction, and decreased as an early response to feeding, before increasing to a peak at 14 days,corresponding with a peak in IGF-I expression. IGFBP-4, which contains a putative connective tissue localisation signal, was the only IGFBP constitutively upregulated following feeding, and was positively correlated with IGF-I expression. Together, these data show that switching to fast growth in Atlantic salmon skeletal muscle involves the local upregulation of IGF-I,IGFBP-5.2 and IGFBP-4, with downregulation of IGFBP-2.1.
Physiological and morphological colour change in Antarctic krill, Euphausia superba: a field study in the Lazarev Sea
Authors: Auerswald Lutz , Freier Ulrich , Lopata Andreas , Meyer Bettina 
Published: November 2008

SUMMARY
Antarctic krill, Euphausia superba, is very susceptible to harmful solar radiation because of its unique genetic setup. Exposure occurs in spring to autumn during vertical diel migration and during occasional daytime surface-swarming. We have investigated colour change in Antarctic krill, Euphausia superba, during summer and winter in the Lazarev Sea in response to ultraviolet radiation (UVR) and photosynthetically active radiation (PAR). Short-term physiological colour change and long-term(seasonal) morphological colour change are present. Both are facilitated by a single type of monochromatic red chromatophore, i.e. erythrophores, of 20–450 μm diameter. Superficial erythrophores cover large dorsal areas, especially above vital organs (brain, sinus glands), additional`profound' erythrophores cover internal organs (heart, gut, nerve cords). Short-term change in light regime causes rapid physiological colour change along dense bundles of microtubules: pigment disperses into chromorhizae upon exposure to PAR and UVA and to a lesser extent to UVB. Darkness leads to aggregation of pigment in the centre and hence blanching. There is no circadian rhythm in the dispersal state of erythrophores present in winter. Physiological colour change in adult krill is two to three times more rapid in summer than in winter. Furthermore, seasonal changes in light regime also result in a profound morphological colour change: in summer animals, abdominal astaxanthin concentration is 450% and erythrophore count is 250–480%higher than in winter krill. We conclude from our results, that pigmentation of E. superba serves in the protection from harmful solar radiation and is adapted to the varying diel and seasonal light conditions.
Lack of Observed Association between High Plasma Osteoprotegerin Concentrations and Ischemic Stroke Risk in a Healthy Population
Authors: Nybo Mads , Johnsen Søren P , Dethlefsen Claus , Overvad Kim , Tjønneland Anne , Jørgensen Jens Otto L , Rasmussen Lars Melholt 
Published: November 2008

Abstract
Background: Several studies suggest that osteoprotegerin (OPG) concentrations may be associated with the risk of ischemic stroke, but no large prospective studies have been conducted. We conducted a nested case-control study within a large cohort to elucidate a possible relation.
Methods: The study was done within a follow-up study including 57 053 men and women. Baseline data included OPG concentrations, lifestyle factors, and medical history. Median length of follow-up was 3.1 years. We assessed the relationship between OPG and stroke risk using conditional logistic regression to adjust for known risk factors (smoking, blood pressure, cholesterol, diabetes, body mass index, alcohol use, polyunsaturated fatty acids, and education).
Results: We identified 254 cases with verified incident acute ischemic stroke and 254 age- and sex-matched controls. Median plasma OPG concentration among cases was 1.84 μg/L (25th–75th percentile 1.45–2.30 μg/L) compared with 1.87 μg/L (1.49–2.27 μg/L) in the control group. The adjusted odds ratio was 0.87 (95% CI 0.46–1.63) comparing participants in the highest quartile of OPG concentrations with those in the lowest quartile.
Conclusions: These findings provide no support for the hypothesis that plasma OPG concentrations are associated with an increased risk of ischemic stroke. This result could indicate a different pathogenic process in stroke development from that in ischemic heart disease, where OPG is a strong predictor.