bluuebunny/crossref_metadata_2025 huggingface dataset:
Locomotor behavior across an environmental transition in the ropefish,Erpetoichthys calabaricus
Authors: Pace Cinnamon M. , Gibb Alice C.
Published: January 2011

Many amphibious organisms undergo repeated aquatic to terrestrial transitions during their lifetime; limbless, elongate organisms that make such transitions must rely on axial-based locomotion in both habitats. How is the same anatomical structure employed to produce an effective behavior across such disparate habitats? Here, we examine an elongate amphibious fish, the ropefish (Erpetoichthys calabaricus), and ask: (1) how do locomotor movements change during the transition between aquatic and terrestrial environments and (2) do distantly related amphibious fishes demonstrate similar modes of terrestrial locomotion? Ropefish were examined moving in four experimental treatments (in which the water level was to lowered mimic the transition between environments) that varied from fully aquatic to fully terrestrial. Kinematic parameters (lateral excursion, wavelength, amplitude and frequency) were calculated for points along the midline of the body and compared across treatments. Terrestrial locomotion in the ropefish is characterized by long, slow, large-amplitude undulations down the length of the body; in contrast, aquatic locomotion is characterized by short-wavelength, small-amplitude, high-frequency undulations that gradually increase in an anterior to posterior direction. Experimental treatments with intermediate water levels were more similar to aquatic locomotion in that they demonstrated an anterior to posterior pattern of increasing lateral excursion and wave amplitude, but were more similar to terrestrial locomotion with regard to wavelength, which did not change in an anterior to posterior direction. Finally, the ropefish and another elongate amphibious fish, the eel, consistently exhibit movements characterized by ‘path following’ when moving on land, which suggests that elongate fishes exhibit functional convergence during terrestrial locomotion.
Olfactory lateralization in homing pigeons: a GPS study on birds released with unilateral olfactory inputs
Authors: Gagliardo Anna , Filannino Caterina , Ioalè Paolo , Pecchia Tommaso , Wikelski Martin , Vallortigara Giorgio
Published: January 2011

A large body of evidence has shown that pigeons rely on an olfactory-based navigational map when homing from unfamiliar locations. Previous studies on pigeons released with one nostril occluded highlighted an asymmetry in favour of the right nostril, particularly concerning the initial orientation performance of naïve birds. Nevertheless, all pigeons experiencing only unilateral olfactory input showed impaired homing, regardless of the side of the occluded nostril. So far this phenomenon has been documented only by observing the birds' vanishing bearings. In the present work we recorded the flight tracks of pigeons with previous homing experience equipped with a GPS data logger and released from an unfamiliar location with the right or the left nostril occluded. The analysis of the tracks revealed that the flight path of the birds with the right nostril occluded was more tortuous than that of unmanipulated controls. Moreover, the pigeons smelling with the left nostril interrupted their journey significantly more frequently and displayed more exploratory activity than the control birds, e.g. during flights around a stopover site. These data suggest a more important involvement of the right olfactory system in processing the olfactory information needed for the operation of the navigational map.
The mechanics of explosive dispersal and self-burial in the seeds of the filaree, Erodium cicutarium (Geraniaceae)
Authors: Evangelista Dennis , Hotton Scott , Dumais Jacques
Published: January 2011

The filaree (Erodium cicutarium), a small, flowering plant related to geraniums, possesses a unique seed dispersal mechanism: the plant can fling its seeds up to half a meter away; and the seeds can bury themselves by drilling into the ground, twisting and untwisting in response to changes in humidity. These feats are accomplished using awns, helical bristles of dead but hygroscopically active tissue attached to the seeds. Here, we describe the kinematics of explosive dispersal and self-burial based on detailed high-speed and time-lapse videos. We use these observations to develop a simple mechanical model that accounts for the coiling behavior of the awn and allows comparison of the strain energy stored in the awn with the kinetic energy at launch. The model is used to examine tradeoffs between dispersal distance and reliability of the dispersal mechanism. The mechanical model may help in understanding the invasive potential of this species and provides a framework for examining other evolutionary tradeoffs in seed dispersal mechanisms among the Geraniaceae.
Colour blindness of the movement-detecting system of the spider Cupiennius salei
Authors: Orlando Eva , Schmid Axel
Published: January 2011

The nocturnal wandering spider Cupiennius salei has one pair of principal eyes and three pairs of secondary eyes located on the prosoma, which differ in both morphology and function. Their spectral sensitivity, measured with intracellular recordings, is due to three different types of photoreceptors with absorbance maxima in the mid-range of the spectrum, at 480 nm and 520 nm and in the UV at 360 nm. Based on these physiological data colour vision might be possible. In the present study, the ability to discriminate coloured moving stimuli from grey backgrounds was tested. The perception of moving coloured stripes in front of backgrounds with 29 different grey levels was measured by using extracellular recordings from the anterior median eye muscles as a monitoring system. Each of these eyes has two muscles, which increase their activity when moving stimuli are presented in front of a secondary eye. This variation in eye muscle activity can be recorded extracellulary in a living spider using a single channel telemetry device. If colour perception exists, the animal should be able to detect a moving coloured stripe in front of any grey level. Blue, green and red stripes were used as moving stimuli, in front of all 29 grey backgrounds. The results indicate that C. salei is not able to discriminate the coloured stimuli from distinct shades of grey. It is therefore evident that the movement-detecting system in this spider appears to be colour blind.
Effect of Ru and Pt Addition over Plate-type Catalysts for Methane Steam Reforming during Daily Start-up and Shut-down
Authors: Guo Yu , Zhou Lu , Zhao Wen , Chen Jian , Sakurai Makoto , Kameyama Hideo
Published: January 2011

A plate-type anodic-alumina-supported 17.9 wt % Ni catalyst quickly deactivated in daily start-up and shut-down (DSS) steam reforming of methane at 700 °C. When 0.05 wt % Ru or Pt was doped, the catalyst exhibited self-activation, self-regeneration, and self-redispersion. The Pt–Ni catalyst showed better stability than Ru–Ni. A wave-shape Pt–Ni catalyst was prepared, while 3000 h continual and 500-time DSS stability was achieved. Nevertheless, for industrial application, some effort should be made to suppress the catalyst sintering.
Application of Tripodal Linker Units to Immobilized Rhodium Complex Catalysts for Asymmetric Hydrogenation
Authors: Fukaya Norihisa , Onozawa Shun-ya , Ueda Masae , Miyaji Takayuki , Takagi Yukio , Sakakura Toshiyasu , Yasuda Hiroyuki
Published: January 2011

The tripodal linker unit with one bromopropyl group and three anchoring silicon atoms was used to immobilize a chiral phosphine–rhodium complex catalyst on an ordered mesoporous silica support. The rhodium and phosphorus leaching levels into the reaction solution after asymmetric hydrogenation were lower for this catalyst than for immobilized catalysts prepared using conventional triethoxysilane.
Preparation and Intercalation Properties of Novel Layered Zinc 1,3,5-Benzenetriphosphonates Composed of Anionic Hybrid Layers
Authors: Maeda Kazuyuki , Hatasawa Haruna , Kawawa Kanako , Nagayoshi Naoko , Matsushima Yuta
Published: January 2011

Zinc 1,3,5-benzenetriphosphonates (ZBP) prepared in the presence of organic cations contain unique layers composed of inorganic 1D chains bridged with benzene rings. ZBP showed intercalation and cation-exchange properties while retaining the layer structure, resembling layered metal phosphates rather than conventional layered phosphonates.
What is the best predictor of the atherogenic LDL subclass phenotype ‘pattern B’ in patients with type 2 diabetes mellitus?
Authors: King R I , Florkowski C M , Yeo J , Walmsley T A , Shand B I , Scott R S , George P M
Published: January 2011

Background

The atherogenic lipoprotein phenotype ‘pattern B’ comprises a predominance of small-dense low-density lipoprotein (sdLDL). Gradient gel electrophoresis (GGE) is considered a ‘gold standard’ method for identifying this phenotype, but is impractical for routine laboratory use. The low-density lipoprotein cholesterol:apolipoprotein-B (LDL-C:Apo-B) ratio has been advocated as a surrogate marker for sdLDL and a direct assay for sdLDL has recently become available. We compared the sdLDL assay and LDL-C:Apo-B with more established lipid parameters to predict the presence of ‘pattern B’ phenotype.

Method

Blood was collected from 97 fasted subjects on three separate occasions. Total cholesterol, triglyceride, Apo-B and sdLDL were measured; LDL- and HDL-cholesterol were determined after ultracentrifugation. The predominant LDL particle size and phenotype were assigned by GGE.

Results

‘Pattern B’ phenotype was identified in 36% of samples. Peak particle size showed a positive correlation with HDL-cholesterol and a negative correlation with triglyceride and Apo-B. Receiver operating curve (ROC) analysis showed triglyceride:HDL-C ratio and triglyceride alone to be the best predictors of ‘pattern B’ phenotype, with area under the curve (AUC) being 0.87 and 0.84, respectively. AUCs for sdLDL (0.74) and LDL-C:Apo-B (0.71) were significantly lower ( P < 0.05). A high sdLDL concentration had the greatest specificity (95%) and positive predictive value (74%) for ‘pattern B’ phenotype, but low sensitivity (43%).

Conclusion

Direct measurement of sdLDL provided the most specific predictor of ‘pattern B’ phenotype, whereas triglyceride:HDL-C ratio or triglycerides alone, parameters readily available in most laboratories, were the best predictors by ROC analysis.
New Plant Venture Performance Differences Among Incumbent, Diversifying, and Entrepreneurial Firms: The Impact of Industry Learning Intensity
Authors: Balasubramanian Natarajan
Published: January 2011

Prior firm experience, firm capabilities, and the industry environment are known to be important determinants of new-venture performance. We hypothesize that firm experience prior to setting up a new venture influences the ability to learn from experience after start-up (which is a key capability), and that this relationship is moderated by the importance of learning by doing within the new venture's industry (which is a critical aspect of the industry environment). We argue that together, these relationships influence performance differences among new plant ventures of incumbents, diversifying entrants, and entrepreneurial (de novo) entrants. Using data on 47,915 new plant ventures in U.S. manufacturing, we find that incumbents and diversifying entrants establish significantly more productive new plants than de novo entrants, and that this advantage significantly increases with the importance of learning by doing in an industry (industry learning intensity). These productivity differences appear to be driven more by learning subsequent to plant start-up than by initial disparities in productivity. Together, these findings strongly suggest that pre-start-up experience adds to the process of post-start-up learning, and that the industry learning environment plays an important role in whether entrepreneurial firms can achieve a competitive advantage over existing firms.

This paper was accepted by Lee Fleming, entrepreneurship.
Ab Initio Electron Diffraction Structure Analysis of Zeolites – Direct Methods Determination of NaY
Authors: Dorset Douglas L. , Gilmore Christopher J.
Published: January 2011

The crystal structure of NaY was re-determined in space group Fd-3m from 87 unique electron diffraction amplitudes obtained at 1250 kV by A. Carlsson, et al. (Chem. Eur. J. 5 (1999) 244), where a = 24.7 Å. The determination, based on maximum entropy and likelihood (computer program MICE), leads to a clearly resolved structure, in contrast to the use of crystallographic phases derived from the Fourier transforms of experimental high-resolution images cited in the above paper. Potential maps from a trial solution contain density sites that correspond closely to the known T-site locations of this FAU framework. Although only framework T-site positions and not linkage oxygens are observed in the map, they can be linked with theoretical oxygens. Subsequent distance least squares (DLS) refinement of the linked model converges to a complete framework structure very close to the one found in earlier X-ray diffraction studies. Contrasting to the earlier study, where no counterion positions were identified, two possible Na positions were clearly visible in the direct phasing map One of these corresponds to a site postulated in previous studies. The other is near a site proposed in a separate electron microscopic/electron diffraction study of Na,FeY. Least squares refinement verifies the former position while eliminating the latter. On the other hand, a separate direct analysis of a dataset from the Y zeolite containing both Na and Fe (Carlsson et al., loc. cit.) was not successful, owing to the smaller number of recorded amplitudes.
Erasmus Darwin, 18th-Century Polymath
Authors: Kormondy Edward J.
Published: January 2011

Erasmus Darwin was a founding member of the Lunar Society of Birmingham, the members of which were referred to as “Lunaticks.” He is here described as a polymath, an 18th-century “natural philosopher” who was a physician, scientist (with interests in botany, zoology, meteorology, chemistry, among others), inventor, and poet who also advanced quite profound evolutionary ideas two generations prior to those of his grandson, Charles Robert Darwin.
Teaching Biodiversity & Evolutionary Biology in a North American Marine Coastal Environment
Authors: Kvist Sebastian , Montanari Shaena A , Yi Hongyu , Fuks Bella , Siddall Mark E.
Published: January 2011

The oceans are among the most biodiverse of Earth's environments. Introducing students to this diversity in the field provides an opportunity to examine the evolution of animals. We detail how readily a field-based biodiversity and evolution class can be designed and taught in a phyletically diverse marine setting in North America.
Engaging Students in Natural Variation in the Introductory Biology Laboratory via a Statistics-based Inquiry Approach
Authors: Thompson E. David , Bowling Bethany V. , Whitson Maggie , Naczi Robert F. C.
Published: January 2011

Natural variation, including the continual selective pressures that lead to speciation, is one of the more dynamic aspects of biology. However, traditional instruction on the topic is often passive in nature, leaving little opportunity for scientific inquiry. In this laboratory exercise, we use a statistics-based, guided-inquiry approach to engage students in natural variation. Students are introduced to speciation and classification by using a dichotomous key to identify various common local trees on the basis of leaf characteristics. Once the students have learned characteristics useful for identification, they are given two leaf samples, a sugar maple and an “unknown.” They are asked to choose characteristics and collect quantitative data in order to determine whether the unknown is a sugar maple. Before data collection, students form hypotheses related to the identity of their unknown, followed by statistical comparison of means to support or refute their original hypotheses. In this way, students gain an appreciation for the activities undertaken by taxonomists that are related to natural variation and classification.
Helping Students Conceptualize Species Divergence Events Using the Online Tool “TimeTree: The Timescale of Life”
Authors: Metzger Kelsey J.
Published: January 2011

Misinformation, preconceptions, and the human perception of time (e.g., in seconds, minutes, days, and years) are factors that can contribute to difficulties experienced by students trying to understand evolutionary phenomena on the scale of geological or “deep” time. In addition to other approaches, the use of a simple online species-divergence estimate calculator, “TimeTree: The Timescale of Life,” can add resolution and clarity to big ideas that sometimes stand in the way of students' understanding of the unifying theory in biology, evolution.
Hemorheological changes and their clinical relevance in preeclampsia
Authors: Fodor Andrea , Győrffy András , Orosz László , Major Tamás
Published: January 2011

This review summarizes the hemorheological changes during gestation and their clinical relevance in preeclampsia. The gestational disease named preeclampsia, characterized by proteinuria (more than 0.3 g/day) and hypertension (blood pressure above 140/90 mmHg), exists from the 20th gestational week until the sixth post partum week. Its etiology is complex; the pathomechanism mainly involves disturbances in cross talks among the vegetative system, the placenta and the circulatory system. Soluble factors of placenta mediate circulatory changes, which result in adaptive responses in both vegetative and circulatory systems. Derailment of this adaption, however, leads to increased turbulence and local damages in cellular elements of the circulatory system. The initial local lesion progresses to a generalized form. Later, these events will continue to strengthen their own cycle. As a result, an unstable circulatory state will be established, which causes organ damages. Orv. Hetil., 2011, 152, 205–211.
Grillage analysis of cellular decks with inclined webs
Authors: Mozos Carlos M. , Aparicio Ángel C.
Published: January 2011

Although grillage analysis is a very popular method for obtaining the response of flat slabs and bridge decks, there are very few guidelines on how to apply the method to decks with inclined webs. This paper presents new and more accurate criteria for obtaining the torsion constant of longitudinal and transverse grillage beams and for splitting a deck into longitudinal beams. These criteria are applied in a numerical study of three different decks with inclined webs. The static response of the numerical models under three load cases is compared with the response of three-dimensional finite-element numerical models.
A novel statistical method for classifying habitat generalists and specialists
Authors: Chazdon Robin L. , Chao Anne , Colwell Robert K. , Lin Shang-Yi , Norden Natalia , Letcher Susan G. , Clark David B. , Finegan Bryan , Arroyo J. Pablo
Published: January 2011

We develop a novel statistical approach for classifying generalists and specialists in two distinct habitats. Using a multinomial model based on estimated species relative abundance in two habitats, our method minimizes bias due to differences in sampling intensities between two habitat types as well as bias due to insufficient sampling within each habitat. The method permits a robust statistical classification of habitat specialists and generalists, without excluding rare species a priori. Based on a user‐defined specialization threshold, the model classifies species into one of four groups: (1) generalist; (2) habitat A specialist; (3) habitat B specialist; and (4) too rare to classify with confidence. We illustrate our multinomial classification method using two contrasting data sets: (1) bird abundance in woodland and heath habitats in southeastern Australia and (2) tree abundance in second‐growth (SG) and old‐growth (OG) rain forests in the Caribbean lowlands of northeastern Costa Rica. We evaluate the multinomial model in detail for the tree data set. Our results for birds were highly concordant with a previous nonstatistical classification, but our method classified a higher fraction (57.7%) of bird species with statistical confidence. Based on a conservative specialization threshold and adjustment for multiple comparisons, 64.4% of tree species in the full sample were too rare to classify with confidence. Among the species classified, OG specialists constituted the largest class (40.6%), followed by generalist tree species (36.7%) and SG specialists (22.7%). The multinomial model was more sensitive than indicator value analysis or abundance‐based phi coefficient indices in detecting habitat specialists and also detects generalists statistically. Classification of specialists and generalists based on rarefied subsamples was highly consistent with classification based on the full sample, even for sampling percentages as low as 20%. Major advantages of the new method are (1) its ability to distinguish habitat generalists (species with no significant habitat affinity) from species that are simply too rare to classify and (2) applicability to a single representative sample or a single pooled set of representative samples from each of two habitat types. The method as currently developed can be applied to no more than two habitats at a time.
Income Distribution, Search and Market Efficiency
Authors: Simhon Avi , Fishman Arthur
Published: January 2011

This paper explores the relationship between income distribution, prices, production efficiency and aggregate output in a decentralized search economy. We show that income distribution determines how competitive prices are and thereby affects production efficiency and aggregate output. It is shown that, under reasonable assumptions, it is possible to engineer a judicious transfer of income from high to low income individuals, which increases income equality, leads to more competitive prices, and increases aggregate output.
Determination of plutonium temperature using the special trans functions theory
Authors: Perovic Slavica , Bauk Sanja
Published: January 2011

The problem of estimating plutonium temperature by an iterative procedure
based on the special trans functions theory has been studied in some detail.
In theory, the differential linear plutonium temperature equation can be
effectively reduced to a non-linear functional transcendental equation
solvable by special trans functions theory. This approach is practically
invariant under the starting plutonium temperature value. This is
significant, because the said iterative special trans functions theory does
not depend on the password data of the plutonium cargo. Obtained numerical
results and graphical simulations confirm the applicability of such approach.
Impact of forward emitter current gain and geometry of pnp power transistors on radiation tolerance of voltage regulators
Authors: Vukic Vladimir , Osmokrovic Predrag
Published: January 2011

Low-dropout voltage regulators with various geometries and technological
realisations of serial pnp power transistors were exposed to ionizing
radiation. Although devices with vertical emitters were considered much less
susceptible to the influence of radiation on forward emitter current gain
than circuits with round emitters, the experiment showed a similar
degradation of current gain in both cases. The main reason of high radiation
susceptibility of the examined vertical serial pnp transistor is the
implementation of an interdigitated emitter, with high perimeter-to-area
ratio, causing the great increase of serial transistor?s base current, but a
minor influence on the maximum output current. Transistors with round
emitters with small perimeter-to-area ratio expressed a moderate current gain
degradation, but a rapid fall of the emitter injection efficiency, causing a
significant decrease of the maximum output current. Regardless of the similar
forward emitter current gain degradation, reliability and operational
characteristics of two types of low-dropout voltage regulators were
completely different.
Natural ionizing radiation and human health in Serbia
Authors: Obradovic-Arsic Danijela , Nenadovic Snezana , Filipovic Dejan , Mihajlovic Bojana
Published: January 2011

This paper provides information about potential effects of natural ionizing
radiation on general population health. Natural radionuclides are
particularly stressed, as well as health effects of high and lower doses.
Radio-ecological areals have been presented for Serbia, while radiation risk
has been assessed for the population of Serbia according to census years.
Radiation dose and risk assessment in hysterosalpingography
Authors: Plecas Darko , Zivkovic Monika , Ciraj-Bjelac Olivera
Published: January 2011

Hysterosalpingography is an important diagnostic method for the evaluation of
the female reproductive tract involving the exposure of patients to ionizing
radiation. The irradiation of ovaries is unavoidable and radiation exposure
of the patient and the associated radiological risk for the foetus and born
child during the period of growth should be considered, as well. The purpose
of this work is to evaluate organ and patient doses and radiation risks
during hysterosalpingography procedures performed in a dedicated
gynecological hospital. The entrance surface air kerma was measured for a
total of 31 patients during hysterosalpingography. Based on the results
obtained, the radiogenic risk for hereditary effects and cancer induction was
estimated. The patient dose levels are in the range of 3-15 mGy, with a
median value of 10 mGy, in terms of entrance surface air kerma. Estimated
median ovarian and uterus doses are 1.7 and 2.3 mGy, respectively. The risk
for fatal cancer and hereditary effects is estimated to be 5.5?10-5 and 3.4
?10-6, respectively. Although low compared to the natural incidence of
genetic effects and cancer, it can be elevated in cases of prolonged or
repeated procedures or procedures where the non-optimized protocol is used.
The Expression and Function of Glucose-Dependent Insulinotropic Polypeptide in the Embryonic Mouse Pancreas
Authors: Prasadan Krishna , Koizumi Masayuki , Tulachan Sidhartha , Shiota Chiyo , Lath Nikesh , Paredes Jose , Guo Ping , El-Gohary Yousef , Malek Marcus , Shah Sohail , Gittes George K.
Published: January 2011

OBJECTIVE

Glucose-dependent insulinotropic polypeptide (GIP) is a member of a structurally related group of hormones that also includes glucagon, glucagon-like peptides, and secretin. GIP is an incretin, known to modulate glucose-induced insulin secretion. Recent studies have shown that glucagon is necessary for early insulin-positive differentiation, and a similar role for incretins in regulating embryonic insulin-positive differentiation seems probable. Here we studied the role of GIP signaling in insulin-positive differentiation in the embryonic mouse pancreas.

RESEARCH DESIGN AND METHODS

The ontogeny of the GIP ligand and GIP receptor in the embryonic pancreas was investigated by immunohistochemistry and RT-PCR. GIP signaling was inhibited in cultured embryonic pancreata using morpholine-ring antisense against GIP ligand and receptor, or small interfering RNA (siRNA) for GIP ligand and receptor. Markers of endocrine cells and their progenitors were studied by immunohistochemistry and RT-PCR.

RESULTS

GIP and GIP receptor mRNA were both detected in the embryonic pancreas by embryonic day 9.5 and then persisted throughout gestation. GIP was generally coexpressed with glucagon by immunostaining. The GIP receptor was typically coexpressed with insulin. Morpholine-ring antisense or siRNA against either GIP ligand or GIP receptor both inhibited the differentiation of insulin-positive cells. Inhibition of GIP or its receptor also led to a decrease in the number of Pdx-1–positive and sox9-positive cells in the cultured embryonic pancreas. The number of Pax6- and Nkx2.2-positive cells, representative of developing pancreatic endocrine cells and β-cells, respectively, was also decreased.

CONCLUSIONS

GIP signaling may play a role in early embryonic pancreas differentiation to form insulin-positive cells or β-cells.
A Newly Identified CG301269 Improves Lipid and Glucose Metabolism Without Body Weight Gain Through Activation of Peroxisome Proliferator–Activated Receptor α and γ
Authors: Jeong Hyun Woo , Lee Joo-Won , Kim Woo Sik , Choe Sung Sik , Kim Kyung-Hee , Park Ho Seon , Shin Hyun Jung , Lee Gha Young , Shin Dongkyu , Lee Hanjae , Lee Jun Hee , Choi Eun Bok , Lee Hyeon Kyu , Chung Heekyoung , Park Seung Bum , Park Kyong Soo , Kim Hyo-Soo , Ro Seonggu , Kim Jae Bum
Published: January 2011

OBJECTIVE

Peroxisome proliferator–activated receptor (PPAR)-α/γ dual agonists have been developed to alleviate metabolic disorders. However, several PPARα/γ dual agonists are accompanied with unwanted side effects, including body weight gain, edema, and tissue failure. This study investigated the effects of a novel PPARα/γ dual agonist, CG301269, on metabolic disorders both in vitro and in vivo.

RESEARCH DESIGN AND METHODS

Function of CG301269 as a PPARα/γ dual agonist was assessed in vitro by luciferase reporter assay, mammalian one-hybrid assay, and analyses of PPAR target genes. In vitro profiles on fatty acid oxidation and inflammatory responses were acquired by fatty acid oxidation assay and quantitative (q)RT-PCR of proinflammatory genes. In vivo effect of CG301269 was examined in db/db mice. Total body weight and various tissue weights were measured, and hepatic lipid profiles were analyzed. Systemic glucose and insulin tolerance were measured, and the in vivo effect of CG301269 on metabolic genes and proinflammatory genes was examined by qRT-PCR.

RESULTS

CG301269 selectively stimulated the transcriptional activities of PPARα and PPARγ. CG301269 enhanced fatty acid oxidation in vitro and ameliorated insulin resistance and hyperlipidemia in vivo. In db/db mice, CG301269 reduced inflammatory responses and fatty liver, without body weight gain.

CONCLUSIONS

We demonstrate that CG301269 exhibits beneficial effects on glucose and lipid metabolism by simultaneous activation of both PPARα and PPARγ. Our data suggest that CG301269 would be a potential lead compound against obesity and related metabolic disorders.
Reduction in Basal Nitric Oxide Activity Causes Albuminuria
Authors: Ott Christian , Schneider Markus P. , Delles Christian , Schlaich Markus P. , Schmieder Roland E.
Published: January 2011

OBJECTIVE

The barrier function of the glomerular filter has been studied for decades. Albuminuria reflects a malfunction of this barrier, and in animals dysfunctional endothelial nitric-oxide (NO) synthase results in albuminuria. We aimed to analyze the importance of NO for the glomerular barrier function in humans.

RESEARCH DESIGN AND METHODS

To assess the effect of endothelial dysfunction on albuminuria, we measured the urine albumin-to-creatinine ratio (UACR) both before and after the blockade of NO synthases (NOSs) with systemic infusion of NG-monomethyl-l-arginine (l-NMMA) in two distinct study populations. In population A, 62 hypertensive patients with type 2 diabetes and, in population B, 22 patients with hypercholesterolemia but without hypertension or type 2 diabetes were examined. All subjects had normal renal function.

RESULTS

There was a significant increase in the UACR in response to NOS inhibition with l-NMMA in hypertensive patients with type 2 diabetes (study population A) and in patients with hypercholesterolemia (study population B). Linear regression analyses revealed that the change in mean arterial presssure in response to l-NMMA was not related to the increase in the UACR in response to l-NMMA in either population, even after adjusting for filtration fraction.

CONCLUSIONS

NOS inhibition provokes albuminuria that is unrelated to changes in blood pressure. It is noteworthy that this finding was evident in patient groups prone to endothelial dysfunction and albuminuria. Thus, acute deterioration of endothelial function by reducing NO activity causes an increase in albuminuria.
The Same Chromosome 9p21.3 Locus Is Associated With Type 2 Diabetes and Coronary Artery Disease in a Chinese Han Population
Authors: Cheng Xiang , Shi Lisong , Nie Shaofang , Wang Fan , Li Xiuchun , Xu Chengqi , Wang Pengyun , Yang Baofeng , Li Qingxian , Pan Zhenwei , Li Yue , Xia Hao , Zheng Chenhong , Ke Yuhe , Wu Yanxia , Tang Tingting , Yan Xinxin , Yang Yan , Xia Ni , Yao Rui , Wang Binbin , Ma Xu , Zeng Qiutang , Tu Xin , Liao Yuhua , Wang Qing K.
Published: January 2011

OBJECTIVE

Recent genome-wide association studies (GWAS) revealed that a 9p21.3 locus was associated with type 2 diabetes. In this study, we carried out a large-scale case-control study in the GeneID Chinese Han population to 1) further replicate the association of 9p21.3 type 2 diabetes GWAS single nucleotide polymorphisms (SNPs) and 2) assess the association of these SNPs with coronary artery disease.

RESEARCH DESIGN AND METHODS

Three SNPs (rs2383208, rs10811661, and rs10757283) were genotyped in two GeneID cohorts of 3,167 Chinese Han individuals. Case-control association design was used to determine the association of the SNPs with type 2 diabetes and coronary artery disease. Gensini scores were calculated in the coronary artery disease subjects and were tested for association with the variants. Multivariate logistic regressions were performed on association studies.

RESULTS

The association between two of the three SNPs and type 2 diabetes was replicated in the GeneID population (rs2383208, P = 0.936; rs10811661-T, P = 0.02, odds ratio [OR] = 1.23; rs10757283-C, P = 0.003, OR = 1.30). The same two SNPs also contributed to the risk of coronary artery disease (CAD) (rs10811661-T, P = 0.002, OR = 1.19; rs10757283-C, P = 0.003, OR = 1.18). In addition, rs10757283 was associated with severity of coronary atherosclerosis estimated by the Gensini scoring system (risk allele C, quantitative-trait regression adjusted P = 0.002).

CONCLUSIONS

For the first time to our knowledge, our results indicated that the same 9p21.3 locus, represented by SNPs rs10811661 and rs10757283, contributed to the risk of type 2 diabetes and coronary artery disease in our GeneID Chinese Han population.
Hyperglycemia Activates Caspase-1 and TXNIP-Mediated IL-1β Transcription in Human Adipose Tissue
Authors: Koenen Tim B. , Stienstra Rinke , van Tits Lambertus J. , de Graaf Jacqueline , Stalenhoef Anton F.H. , Joosten Leo A.B. , Tack Cees J. , Netea Mihai G.
Published: January 2011

OBJECTIVE

Obesity is characterized by elevated levels of proinflammatory cytokines, including interleukin (IL)-1β, that contribute to the development of insulin resistance. In this study, we set out to investigate whether hyperglycemia drives IL-1β production and caspase-1 activation in murine and human adipose tissue, thus inducing insulin resistance.

RESEARCH DESIGN AND METHODS

ob/ob animals were used as a model to study obesity and hyperglycemia. Human adipose tissue fragments or adipocytes were cultured in medium containing normal or high glucose levels. Additionally, the role of thioredoxin interacting protein (TXNIP) in glucose-induced IL-1β production was assessed.

RESULTS

TXNIP and caspase-1 protein levels were more abundantly expressed in adipose tissue of hyperglycemic ob/ob animals as compared with wild-type mice. In human adipose tissue, high glucose resulted in a 10-fold upregulation of TXNIP gene expression levels (P < 0.01) and a 10% elevation of caspase-1 activity (P < 0.05), together with induction of IL-1β transcription (twofold, P < 0.01) and a significant increase in IL-1β secretion. TXNIP suppression in human adipocytes, either by a small interfering RNA approach or a peroxisome proliferator–activated receptor-γ agonist, counteracted the effects of high glucose on bioactive IL-1 production (P < 0.01) mainly through a decrease in transcription levels paralleled by reduced intracellular pro-IL-1β levels.

CONCLUSIONS

High glucose activates caspase-1 in human and murine adipose tissue. Glucose-induced activation of TXNIP mediates IL-1β mRNA expression levels and intracellular pro-IL-1β accumulation in adipose tissue. The concerted actions lead to enhanced secretion of IL-1β in adipose tissue that may contribute to the development of insulin resistance.
Progression of Carotid Artery Intima-Media Thickness During 12 Years in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study
Authors: Polak Joseph F. , Backlund Jye-Yu C. , Cleary Patricia A. , Harrington Anita P. , O’Leary Daniel H. , Lachin John M. , Nathan David M. ,   for the DCCT/EDIC Research Group
Published: January 2011

OBJECTIVE

This study investigated the long-term effects of intensive diabetic treatment on the progression of atherosclerosis, measured as common carotid artery intima-media thickness (IMT).

RESEARCH DESIGN AND METHODS

A total of 1,116 participants (52% men) in the Epidemiology of Diabetes Interventions and Complications (EDIC) trial, a long-term follow-up of the Diabetes Control and Complications Trial (DCCT), had carotid IMT measurements at EDIC years 1, 6, and 12. Mean age was 46 years, with diabetes duration of 24.5 years at EDIC year 12. Differences in IMT progression between DCCT intensive and conventional treatment groups were examined, controlling for clinical characteristics, IMT reader, and imaging device.

RESULTS

Common carotid IMT progression from EDIC years 1 to 6 was 0.019 mm less in intensive than in conventional (P < 0.0001), and from years 1 to 12 was 0.014 mm less (P = 0.048); but change from years 6 to 12 was similar (intensive − conventional = 0.005 mm, P = 0.379). Mean A1C levels during DCCT and DCCT/EDIC were strongly associated with progression of IMT, explaining most of the differences in IMT progression between DCCT treatment groups. Albuminuria, older age, male sex, smoking, and higher systolic blood pressure were significant predictors of IMT progression.

CONCLUSIONS

Intensive treatment slowed IMT progression for 6 years after the end of DCCT but did not affect IMT progression thereafter (6–12 years). A beneficial effect of prior intensive treatment was still evident 13 years after DCCT ended. These differences were attenuated but not negated after adjusting for blood pressure. These results support the early initiation and continued maintenance of intensive diabetes management in type 1 diabetes to retard atherosclerosis.
Selective Reversible Inhibition of Liver Carnitine Palmitoyl-Transferase 1 by Teglicar Reduces Gluconeogenesis and Improves Glucose Homeostasis
Authors: Conti Roberto , Mannucci Edoardo , Pessotto Pompeo , Tassoni Emanuela , Carminati Paolo , Giannessi Fabio , Arduini Arduino
Published: January 2011

OBJECTIVE

We have developed a new antihyperglycemic agent (teglicar) through the selective and reversible inhibition of the liver isoform of carnitine palmitoyl-transferase 1 (L-CPT1).

RESEARCH DESIGN AND METHODS

Glucose production was investigated in isolated hepatocytes and during pancreatic clamps in healthy rats. Chronic treatments on C57BL/6J, db/db, high-fat fed mice, and rats were performed to understand glucose metabolism and insulin sensitivity.

RESULTS

In isolated hepatocytes, teglicar concentration dependently reduced ketone bodies and glucose production up to 72 and 50%, respectively. In rats, teglicar reduced the endogenous glucose production (−62%) without affecting peripheral glucose utilization. Heart 2-[3H]deoxyglucose uptake in mice was also not affected, confirming in vivo the drug selectivity toward L-CPT1. Chronic treatment in db/db mice (50 mg/kg/bid; 45 days) reduced postabsorptive glycemia (−38%), water consumption (−31%), and fructosamine (−30%). Such antidiabetic activity was associated with an improved insulin sensitivity assessed by the insulin tolerance test. A significant 50% increase in hepatic triglyceride content (HTGC) was found, although plasma alanineaminotransferase was not altered. In addition, long-term teglicar administration to high-fat fed C57BL/6J mice normalized glycemia (−19%) and insulinemia (−53%). Long-term teglicar administration (30 days, 80 mg/kg) in healthy overnight-fasted rats slightly reduced basal glycemia (−20%, ns), reduced basal insulin levels by 60%, doubled triglycerides, and increased free-fatty acids (+53%). HTGC was markedly increased, but liver and peripheral insulin sensitivity assessed by hyperinsulinemiceuglycemic clamp were not affected.

CONCLUSIONS

Teglicar, in vitro and in animal models, reduces gluconeogenesis and improves glucose homeostasis, refreshing the interest in selective and reversible L-CPT1 inhibition as a potential antihyperglycemic approach.
Participation of Hindbrain AMP-Activated Protein Kinase in Glucoprivic Feeding
Authors: Li Ai-Jun , Wang Qing , Ritter Sue
Published: January 2011

OBJECTIVE

To examine the role of AMP-activated protein kinase (AMPK) in the control of glucoprivic feeding by hindbrain catecholamine neurons.

RESEARCH DESIGN AND METHODS

Micropunched hindbrain samples were collected from control and 2-deoxy-d-glucose (2DG)-injected rats for Western blot analysis of phosphorylated (activated) AMPK (pAMPK). Samples also were collected from 2DG-injected rats pretreated with anti-dopamine-β-hydroxylase conjugated to saporin to lesion hindbrain catecholamine neurons. In a second experiment, rats were given a fourth-ventricle injection of compound C (CC) or 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR), an inhibitor and activator of AMPK, to identify a role for AMPK in hindbrain neurons required for elicitation of 2DG-induced feeding.

RESULTS

Systemic 2DG stimulated food intake in controls but not in catecholamine-lesioned rats. In controls, but not catecholamine-lesioned rats, 2DG also increased phosphorylated Thr172 at AMPKα subunits (pAMPKα) in hindbrain micropunches containing catecholaminergic cell groups A1 through the middle region of C1 (A1–C1m). Increased pAMPKα was not observed in the adjacent noncatecholaminergic ventromedial medulla or in the A2–C2 catecholamine cell groups in the dorsal hindbrain. Fourth-ventricle injection of CC attenuated 2DG-induced feeding during the first 2 h of the test, and AICAR alone increased food intake only during the first 60 min of the 4-h test.

CONCLUSIONS

Results indicate that AMPK in catecholaminergic A1–C1m neurons is activated by glucoprivation. Therefore, AMPK may contribute to the glucose-sensing mechanism by which these neurons detect and signal a glucose deficit in the service of systemic glucoregulation.
Resveratrol Improves Oxidative Stress and Protects Against Diabetic Nephropathy Through Normalization of Mn-SOD Dysfunction in AMPK/SIRT1-Independent Pathway
Authors: Kitada Munehiro , Kume Shinji , Imaizumi Noriko , Koya Daisuke
Published: January 2011

OBJECTIVE

Despite the beneficial effects of resveratrol (RSV) on cardiovascular disease and life span, its effects on type 2 diabetic nephropathy remain unknown. This study examined the renoprotective effects of RSV in db/db mice, a model of type 2 diabetes.

RESEARCH DESIGN AND METHODS

db/db mice were treated with RSV (0.3% mixed in chow) for 8 weeks. We measured urinary albumin excretion (UAE), histological changes (including mesangial expansion, fibronectin accumulation, and macrophage infiltration), oxidative stress markers (urinary excretion and mitochondrial content of 8-hydroxy-2'-deoxyguanosine [8-OHdG], nitrotyrosine expression), and manganese-superoxide dismutase (Mn-SOD) activity together with its tyrosine-nitrated modification and mitochondrial biogenesis in the kidney. Blood glucose, glycated hemoglobin, and plasma lipid profiles were also measured. The phosphorylation of 5′-AMP–activated kinase (AMPK) and expression of silent information regulator 1 (SIRT1) in the kidney were assessed by immunoblotting.

RESULTS

RSV significantly reduced UAE and attenuated renal pathological changes in db/db mice. Mitochondrial oxidative stress and biogenesis were enhanced in db/db mice; however, Mn-SOD activity was reduced through increased tyrosine-nitrated modification. RSV ameliorated such alterations and partially improved blood glucose, glycated hemoglobin, and abnormal lipid profile in db/db mice. Activation of AMPK was decreased in the kidney of db/db mice compared with db/m mice. RSV neither modified AMPK activation nor SIRT1 expression in the kidney.

CONCLUSIONS

RSV ameliorates renal injury and enhanced mitochondrial biogenesis with Mn-SOD dysfunction in the kidney of db/db mice, through improvement of oxidative stress via normalization of Mn-SOD function and glucose-lipid metabolism. RSV has antioxidative activities via AMPK/SIRT1-independent pathway.
Glucagon Receptor Knockout Prevents Insulin-Deficient Type 1 Diabetes in Mice
Authors: Lee Young , Wang May-Yun , Du Xiu Quan , Charron Maureen J. , Unger Roger H.
Published: January 2011

OBJECTIVE

To determine the role of glucagon action in the metabolic phenotype of untreated insulin deficiency.

RESEARCH DESIGN AND METHODS

We compared pertinent clinical and metabolic parameters in glucagon receptor-null (Gcgr−/−) mice and wild-type (Gcgr+/+) controls after equivalent destruction of β-cells. We used a double dose of streptozotocin to maximize β-cell destruction.

RESULTS

Gcgr+/+ mice became hyperglycemic (>500 mg/dL), hyperketonemic, polyuric, and cachectic and had to be killed after 6 weeks. Despite comparable β-cell destruction in Gcgr−/− mice, none of the foregoing clinical or laboratory manifestations of diabetes appeared. There was marked α-cell hyperplasia and hyperglucagonemia (∼1,200 pg/mL), but hepatic phosphorylated cAMP response element binding protein and phosphoenolpyruvate carboxykinase mRNA were profoundly reduced compared with Gcgr+/+ mice with diabetes—evidence that glucagon action had been effectively blocked. Fasting glucose levels and oral and intraperitoneal glucose tolerance tests were normal. Both fasting and nonfasting free fatty acid levels and nonfasting β-hydroxy butyrate levels were lower.

CONCLUSIONS

We conclude that blocking glucagon action prevents the deadly metabolic and clinical derangements of type 1 diabetic mice.
SUMOylation Regulates Insulin Exocytosis Downstream of Secretory Granule Docking in Rodents and Humans
Authors: Dai Xiao-Qing , Plummer Greg , Casimir Marina , Kang Youhou , Hajmrle Catherine , Gaisano Herbert Y. , Manning Fox Jocelyn E. , MacDonald Patrick E.
Published: January 2011

OBJECTIVE

The reversible attachment of small ubiquitin-like modifier (SUMO) proteins controls target localization and function. We examined an acute role for the SUMOylation pathway in downstream events mediating insulin secretion.

RESEARCH DESIGN AND METHODS

We studied islets and β-cells from mice and human donors, as well as INS-1 832/13 cells. Insulin secretion, intracellular Ca2+, and β-cell exocytosis were monitored after manipulation of the SUMOylation machinery. Granule localization was imaged by total internal reflection fluorescence and electron microscopy; immunoprecipitation and Western blotting were used to examine the soluble NSF attachment receptor (SNARE) complex formation and SUMO1 interaction with synaptotagmin VII.

RESULTS

SUMO1 impairs glucose-stimulated insulin secretion by blunting the β-cell exocytotic response to Ca2+. The effect of SUMO1 to impair insulin secretion and β-cell exocytosis is rapid and does not require altered gene expression or insulin content, is downstream of granule docking at the plasma membrane, and is dependent on SUMO-conjugation because the deSUMOylating enzyme, sentrin/SUMO-specific protease (SENP)-1, rescues exocytosis. SUMO1 coimmunoprecipitates with the Ca2+ sensor synaptotagmin VII, and this is transiently lost upon glucose stimulation. SENP1 overexpression also disrupts the association of SUMO1 with synaptotagmin VII and mimics the effect of glucose to enhance exocytosis. Conversely, SENP1 knockdown impairs exocytosis at stimulatory glucose levels and blunts glucose-dependent insulin secretion from mouse and human islets.

CONCLUSIONS

SUMOylation acutely regulates insulin secretion by the direct and reversible inhibition of β-cell exocytosis in response to intracellular Ca2+ elevation. The SUMO protease, SENP1, is required for glucose-dependent insulin secretion.