bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence that the Arcuate Nucleus Is an Important Site of Progesterone Negative Feedback in the Ewe
Authors: Goodman Robert L. , Holaskova Ida , Nestor Casey C. , Connors John M. , Billings Heather J. , Valent Miro , Lehman Michael N. , Hileman Stanley M.
Published: June 2011

There is now considerable evidence that dynorphin neurons mediate the negative feedback actions of progesterone to inhibit GnRH and LH pulse frequency, but the specific neurons have yet to be identified. In ewes, dynorphin neurons in the arcuate nucleus (ARC) and preoptic area (POA) are likely candidates based on colocalization with progesterone receptors. These studies tested the hypothesis that progesterone negative feedback occurs in either the ARC or POA by determining whether microimplants of progesterone into either site would inhibit LH pulse frequency (study 1) and whether microimplants of the progesterone receptor antagonist, RU486, would disrupt the inhibitory effects of peripheral progesterone (study 2). Both studies were done in ovariectomized (OVX) and estradiol-treated OVX ewes. In study 1, no inhibitory effects of progesterone were observed during treatment in either area. In study 2, microimplants of RU486 into the ARC disrupted the negative-feedback actions of peripheral progesterone treatments on LH pulse frequency in both OVX and OVX+estradiol ewes. In contrast, microimplants of RU486 into the POA had no effect on the ability of systemic progesterone to inhibit LH pulse frequency. We thus conclude that the ARC is one important site of progesterone-negative feedback in the ewe. These data, which are the first evidence on the neural sites in which progesterone inhibits GnRH pulse frequency in any species, are consistent with the hypothesis that ARC dynorphin neurons mediate this action of progesterone.
Minireview: Intrinsic and Extrinsic Factors in Thyroid Gland Development: An Update
Authors: De Felice Mario , Di Lauro Roberto
Published: June 2011

In vertebrates the portion of the thyroid gland synthesizing the thyroid hormones develops from a small group of endodermal cells in the foregut. The nature of the signals that lead to the biochemical and morphogenetic events responsible for the organization of these cells into the adult thyroid gland has only recently become evident. In this review we summarize recent developments in the understanding of these processes, derived from evidence collected in several organisms.
Mouse Primary Uterine Cell Coculture System Revisited: Ovarian Hormones Mimic the Aspects of in Vivo Uterine Cell Proliferation
Authors: Chung Daesuk , Das Sanjoy K.
Published: June 2011

Previously, the uterine epithelial-stromal coculture system had limited success mimicking in vivo ovarian hormone-dependent cell-specific proliferation. Here, we established a mouse primary uterine coculture system, in which cells collected in pseudopregnancy specifically on d 4 are conducive to supporting hormone-induced cell-specific proliferation. When two cell types are placed in coculture without direct contact via cell culture inserts (nonadjacent), as opposed to with contact (adjacent), epithelial cells exhibit significant proliferation by estradiol-17β (E2), whereas progesterone in combination with E2 caused inhibition of epithelial cell proliferation and a major shift in proliferation from epithelial to stromal cells. Epithelial cell integrity, with respect to E-cadherin expression, persisted in nonadjacent, but not adjacent, conditions. In subsequent studies of nonadjacent cocultures, localization of estrogen receptor (ER)α and progesterone receptor (PR), but not ERβ, appeared to be abundant, presumably indicating that specific ER or PR coregulator expression might be responsible for this difference. Consistently, an agonist of ERα, but not ERβ, was supportive of proliferation, and antagonists of ER or PR totally eliminated cell-specific proliferation by hormones. RT-PCR analyses also revealed that hormone-responsive genes primarily exhibit appropriate regulation. Finally, suppression of immunoglobulin heavy chain binding protein, a critical regulator of ERα signaling, in epithelial and/or stromal cells caused dramatic inhibition of E2-dependent epithelial cell proliferation, suggesting that a molecular perturbation approach is applicable to mimic in vivo uterine control. In conclusion, our established coculture system may serve as a useful alternative model to explore in vivo aspects of cell proliferation via communication between the epithelial and stromal compartments under the direction of ovarian hormones.
Minireview: Hormones and Human Sexual Orientation
Authors: Balthazart Jacques
Published: June 2011

Many people believe that sexual orientation (homosexuality vs. heterosexuality) is determined by education and social constraints. There are, however, a large number of studies indicating that prenatal factors have an important influence on this critical feature of human sexuality. Sexual orientation is a sexually differentiated trait (over 90% of men are attracted to women and vice versa). In animals and men, many sexually differentiated characteristics are organized during early life by sex steroids, and one can wonder whether the same mechanism also affects human sexual orientation. Two types of evidence support this notion. First, multiple sexually differentiated behavioral, physiological, or even morphological traits are significantly different in homosexual and heterosexual populations. Because some of these traits are known to be organized by prenatal steroids, including testosterone, these differences suggest that homosexual subjects were, on average, exposed to atypical endocrine conditions during development. Second, clinical conditions associated with significant endocrine changes during embryonic life often result in an increased incidence of homosexuality. It seems therefore that the prenatal endocrine environment has a significant influence on human sexual orientation but a large fraction of the variance in this behavioral characteristic remains unexplained to date. Genetic differences affecting behavior either in a direct manner or by changing embryonic hormone secretion or action may also be involved. How these biological prenatal factors interact with postnatal social factors to determine life-long sexual orientation remains to be determined.
Targeted Deletion of Adipocytes by Apoptosis Leads to Adipose Tissue Recruitment of Alternatively Activated M2 Macrophages
Authors: Fischer-Posovszky Pamela , Wang Qiong A. , Asterholm Ingrid Wernstedt , Rutkowski Joseph M. , Scherer Philipp E.
Published: June 2011

Obesity is frequently associated with an infiltration of macrophages into adipose tissue. Adipocyte dysfunction causes a phenotypic switch of macrophages from an alternatively activated M2-like phenotype towards a proinflammatory M1 phenotype. The cross talk between adipocytes and infiltrating immune cells, in particular macrophages, is thought to contribute to local and eventually systemic inflammation. Here, we tested the phenotypic impact of a lack of adipocytes on the inflammatory status of macrophages. We took advantage of the fat apoptosis through targeted activation of caspase-8 (FAT-ATTAC) mouse model that allows for the inducible system-wide elimination of adipocytes through a proapoptotic mechanism and followed the degree and type of inflammatory response upon ablation of live adipocytes. Analysis of depots 2 wk after elimination of adipocytes resulted in markedly reduced levels of adipose tissue and a robust down-regulation of circulating adipokines. Quantitative PCR and immunohistochemistry on epididymal and inguinal fat depots revealed an increase of the macrophage markers F4/80 and CD11c. Using polychromatic flow cytometry, we observed an up-regulation of alternatively activated M2 macrophage markers (CD206 and CD301) on the majority of F4/80 positive cells. Apoptosis of adipocytes is sufficient to initiate a large influx of macrophages into the remnant fat pads. However, these macrophages are alternatively activated, antiinflammatory M2 macrophages and not M1 cells. We conclude that adipocyte death is sufficient to initiate macrophage infiltration, and live adipocytes are required to initiate and/or sustain a proinflammatory response within the infiltrating macrophages in adipose tissue.
Protein 4.1R regulates cell adhesion, spreading, migration and motility of mouse keratinocytes by modulating surface expression of β1 integrin
Authors: Chen Lixiang , Hughes Richard A. , Baines Anthony J. , Conboy John , Mohandas Narla , An Xiuli
Published: June 2011

Protein 4.1R is a membrane-cytoskeleton adaptor protein that has diverse roles in controlling the cell surface expression and/or function of transmembrane proteins, and in organizing F-actin. 4.1R is expressed in keratinocytes, but its role in these cells has not been explored. Here, we have investigated the role of 4.1R in skin using 4.1R−/− mice. Cell adhesion, spreading, migration and motility were significantly impaired in 4.1R−/− keratinocytes, and 4.1R−/− mice exhibited defective epidermal wound healing. Cultured 4.1R−/− keratinocytes on fibronectin failed to form actin stress fibres and focal adhesions. Furthermore, in the absence of 4.1R, the surface expression, and consequently the activity of β1 integrin were reduced. These data enabled the identification of a functional role for protein 4.1R in keratinocytes by modulating the surface expression of β1 integrin, possibly through a direct association between 4.1R and β1 integrin.
Wnt5a is a cell-extrinsic factor that supports self-renewal of mouse spermatogonial stem cells
Authors: Yeh Jonathan R. , Zhang Xiangfan , Nagano Makoto C.
Published: June 2011

The maintenance of spermatogonial stem cells (SSCs) provides the foundation for life-long spermatogenesis. Although glial-cell-line-derived neurotrophic factor and fibroblast growth factor 2 are crucial for self-renewal of SSCs, recent studies have suggested that other growth factors have important roles in controlling SSC fate. Because β-catenin-dependent Wnt signaling promotes self-renewal of various stem cell types, we hypothesized that this pathway contributes to SSC maintenance. Using transgenic reporter mice for β-catenin-dependent signaling, we found that this signaling was not active in SSCs in vitro and in most spermatogonia in vivo. Nonetheless, a pan-Wnt antagonist significantly reduced SSC activity in vitro, suggesting that some Wnt molecules exist in our serum-free culture system and contribute to SSC maintenance. Here, we report that Wnt5a promotes SSC activity. We found that Wnt5a-expressing fibroblasts supported SSC activity better than those not expressing Wnt5a in culture, and that recombinant Wnt5a stimulated SSC maintenance. Furthermore, Wnt5a promoted SSC survival in the absence of feeder cells, and this effect was abolished by inhibiting the Jun N-terminal kinase cascade. In addition, Wnt5a blocked β-catenin-dependent signaling. We detected the expression of Wnt5a and potential Wnt5a receptors in Sertoli cells and stem/progenitor spermatogonia, respectively. These results indicate that Wnt5a is a cell-extrinsic factor that supports SSC self-renewal through β-catenin-independent mechanisms.
Rab9-dependent retrograde transport and endosomal sorting of the endopeptidase furin
Authors: Chia Pei Zhi Cheryl , Gasnereau Isabelle , Lieu Zi Zhao , Gleeson Paul A.
Published: June 2011

The endopeptidase furin and the trans-Golgi network protein TGN38 are membrane proteins that recycle between the TGN and plasma membrane. TGN38 is transported by a retromer-dependent pathway from early endosomes to the TGN, whereas the intracellular transport of furin is poorly defined. Here we have identified the itinerary and transport requirements of furin. Using internalisation assays, we show that furin transits the early and late endosomes en route to the TGN. The GTPase Rab9 and the TGN golgin GCC185, components of the late endosome-to-TGN pathway, were required for efficient TGN retrieval of furin. By contrast, TGN38 trafficking was independent of Rab9 and GCC185. To identify the sorting signals for the early endosome-to-TGN pathway, the trafficking of furin–TGN38 chimeras was investigated. The diversion of furin from the Rab9-dependent late-endosome-to-TGN pathway to the retromer-dependent early-endosome-to-TGN pathway required both the transmembrane domain and cytoplasmic tail of TGN38. We present evidence to suggest that the length of the transmembrane domain is a contributing factor in endosomal sorting. Overall, these data show that furin uses the Rab9-dependent pathway from late endosomes and that retrograde transport directly from early endosomes is dependent on both the transmembrane domain and the cytoplasmic tail.
S100B protein regulates myoblast proliferation and differentiation by activating FGFR1 in a bFGF-dependent manner
Authors: Riuzzi Francesca , Sorci Guglielmo , Donato Rosario
Published: June 2011

S100B protein has been shown to exert anti-myogenic and mitogenic effects in myoblast cultures through inhibition of the myogenic p38 MAPK and activation of the mitogenic ERK1/2. However, the receptor mediating these effects had not been identified. Here, we show that S100B increases and/or stabilizes the binding of basic fibroblast growth factor (bFGF) to bFGF receptor 1 (FGFR1) by interacting with bFGF, thereby enhancing FGFR1 activation and the mitogenic and anti-myogenic effects of FGFR1. S100B also binds to its canonical receptor RAGE (receptor for advanced glycation end-products), a multi-ligand receptor previously shown to transduce a pro-myogenic signal when activated by HMGB1, and recruits RAGE into a RAGE–S100B–bFGF–FGFR1 complex. However, when bound to S100B–bFGF–FGFR1, RAGE can no longer stimulate myogenic differentiation, whereas in the absence of either bFGF or FGFR1, binding of S100B to RAGE results in stimulation of RAGE anti-mitogenic and promyogenic signaling. An S100B–bFGF–FGFR1 complex also forms in Rage−/− myoblasts, leading to enhanced proliferation and reduced differentiation, which points to a dispensability of RAGE for the inhibitory effects of S100B on myoblasts under the present experimental conditions. These results reveal a new S100B-interacting protein – bFGF – in the extracellular milieu and suggest that S100B stimulates myoblast proliferation and inhibits myogenic differentiation by activating FGFR1 in a bFGF-dependent manner.
TGFB1 disrupts the angiogenic potential of microvascular endothelial cells of the corpus luteum
Authors: Maroni Dulce , Davis John S.
Published: June 2011

Cyclical formation and regression of the ovarian corpus luteum is required for reproduction. During luteal regression, the microvasculature of the corpus luteum is extensively disrupted. Prostaglandin F2α, a primary signal for luteal regression, induces the expression of transforming growth factor β1 (TGFB1) in the corpus luteum. This study determined the actions of TGFB1 on microvascular endothelial cells isolated from the bovine corpus luteum (CLENDO cells). We hypothesized that TGFB1 participates in the disruption of the microvasculature during luteal regression. TGFB1 activated the canonical SMAD signaling pathway in CLENDO cells. TGFB1 (1 ng/ml) significantly reduced both basal and fetal-calf-serum-stimulated DNA synthesis, without reducing cell viability. TGFB1 also significantly reduced CLENDO cell transwell migration and disrupted the formation of capillary-like structures when CLENDO cells were plated on Matrigel. By contrast, CLENDO cells plated on fibrillar collagen I gels did not form capillary-like structures and TGFB1 induced cell death. Additionally, TGFB1 caused loss of VE-cadherin from cellular junctions and loss of cell–cell contacts, and increased the permeability of confluent CLENDO cell monolayers. These studies demonstrate that TGFB1 acts directly on CLENDO cells to limit endothelial cell function and suggest that TGFB1 might act in the disassembly of capillaries observed during luteal regression.
Real-time monitoring of redox changes in the mammalian endoplasmic reticulum
Authors: van Lith Marcel , Tiwari Shweta , Pediani John , Milligan Graeme , Bulleid Neil J.
Published: June 2011

Redox-sensitive GFPs with engineered disulphide bonds have been used previously to monitor redox status in the cytosol and mitochondria of living cells. The usefulness of these redox probes depends on the reduction potential of the disulphide, with low values suiting the cytosol and mitochondrion, and higher values suiting the more oxidising environment of the endoplasmic reticulum (ER). Here, we targeted a modified redox-sensitive GFP (roGFP1-iL), with a relatively high reduction potential, to the ER of mammalian cells. We showed that the disulphide is partially oxidised, allowing roGFP1-iL to monitor changes in ER redox status. When cells were treated with puromycin, the redox balance became more reducing, suggesting that the release of nascent chains from ribosomes alters the ER redox balance. In addition, downregulating Ero1α prevented normal rapid recovery from dithiothreitol (DTT), whereas downregulating peroxiredoxin IV had no such effect. This result illustrates the contribution of the Ero1α oxidative pathway to ER redox balance. This first report of the use of roGFP to study the ER of mammalian cells demonstrates that roGFP1-iL can be used to monitor real-time changes to the redox status in individual living cells.
KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells
Authors: Tanaka Kousuke , Sugiura Yoshimi , Ichishita Ryohei , Mihara Katsuyoshi , Oka Toshihiko
Published: June 2011

Mitochondria utilize diverse cytoskeleton-based mechanisms to control their functions and morphology. Here, we report a role for kinesin-like protein KLP6, a newly identified member of the kinesin family, in mitochondrial morphology and dynamics. An RNA interference screen using Caenorhabditis elegans led us to identify a C. elegans KLP-6 involved in maintaining mitochondrial morphology. We cloned a cDNA coding for a rat homolog of C. elegans KLP-6, which is an uncharacterized kinesin in vertebrates. A rat KLP6 mutant protein lacking the motor domain induced changes in mitochondrial morphology and significantly decreased mitochondrial motility in HeLa cells, but did not affect the morphology of other organelles. In addition, the KLP6 mutant inhibited transport of mitochondria during anterograde movement in differentiated neuro 2a cells. To date, two kinesins, KIF1Bα and kinesin heavy chain (KHC; also known as KIF5) have been shown to be involved in the distribution of mitochondria in neurons. Expression of the kinesin heavy chain/KIF5 mutant prevented mitochondria from entering into neurites, whereas both the KLP6 and KIF1Bα mutants decreased mitochondrial transport in axonal neurites. Furthermore, both KLP6 and KIF1Bα bind to KBP, a KIF1-binding protein required for axonal outgrowth and mitochondrial distribution. Thus, KLP6 is a newly identified kinesin family member that regulates mitochondrial morphology and transport.
The broad range of contractile behaviour of the avian pectoralis: functional and evolutionary implications
Authors: Jackson Brandon E. , Tobalske Bret W. , Dial Kenneth P.
Published: June 2011

Wing-assisted incline running (WAIR) in birds combines the use of the wings and hindlimbs to ascend otherwise insurmountable obstacles. It is a means of escape in precocial birds before they are able to fly, and it is used by a variety of juvenile and adult birds as an alternative to flight for exploiting complex three-dimensional environments at the interface of the ground and air. WAIR and controlled flapping descent (CFD) are the bases of the ontogenetic-transitional wing hypothesis, wherein WAIR and CFD are proposed to be extant biomechanical analogs for incremental adaptive stages in the evolutionary origin of flight. A primary assumption of the hypothesis is that work and power requirements from the primary downstroke muscle, the pectoralis, incrementally increase from shallow- to steep-angled terrestrial locomotion, and between terrestrial and aerial locomotion. To test this assumption, we measured in vivo force, electromyographic (EMG) activity and length change in the pectoralis of pigeons (Columba livia) as the birds engaged in shallow and steep WAIR (65 and 85 deg, respectively) and in three modes of slow flight immediately following take-off: ascending at 80 deg, level and descending at –60 deg. Mean EMG amplitude, muscle stress, strain, work and power were minimal during shallow WAIR and increased stepwise from steep WAIR to descending flight and level flight to reach the highest levels during ascending flight. Relative to resting length of the pectoralis, fractional lengthening (maximum muscle strain) was similar among behaviors, but fractional shortening (minimum muscle strain) was absent during WAIR such that the pectoralis did not shorten to less than the resting length. These data dramatically extend the known range of in vivo contractile behavior for the pectoralis in birds. We conclude that WAIR remains a useful extant model for the evolutionary transition from terrestrial to aerial locomotion in birds because work and power requirements from the pectoralis increase incrementally during WAIR and from WAIR to flight.
Audiogram of a stranded Blainville's beaked whale (Mesoplodon densirostris) measured using auditory evoked potentials
Authors: Pacini Aude F. , Nachtigall Paul E. , Quintos Christopher T. , Schofield T. David , Look Dera A. , Levine Gregg A. , Turner Jason P.
Published: June 2011

Quantifying and understanding the impact of anthropogenic sound on marine mammals has been the focus of many researchers both in laboratory settings as well as in the field. This study presents the audiogram of a sub-adult Blainville's beaked whale that stranded in Hawaii. The hearing measurements were conducted using the non-invasive auditory brainstem response technique. A total of 11 sinusoidally amplitude modulated tones were tested ranging from 5.6 to 160 kHz. The audiogram data indicated that the region of best hearing was found between 40 and 50 kHz with thresholds below 50 dB. This frequency range partially overlaps with the frequency modulated upsweep that Blainville's beaked whales have been reported to use during echolocation. These results match the frequency range obtained from the hearing measurements of a Gervais' beaked whale previously tested using contact acoustic stimulation and emphasize the importance of obtaining rapid hearing measurements on live stranded animals to improve the understanding of poorly known species.
Variation in metabolic rate ofAnopheles gambiaeandA. arabiensisin a Sahelian village
Authors: Huestis Diana L. , Yaro Alpha S. , Traoré Adama I. , Adamou Abdoulaye , Kassogué Yaya , Diallo Moussa , Timbiné Seydou , Dao Adama , Lehmann Tovi
Published: June 2011

In the Sahel, the Anopheles gambiae complex consists of Anopheles arabiensis and the M and S molecular forms of A. gambiae sensu stricto. However, the composition of these malaria vectors varies spatially and temporally throughout the region and is thought to be linked to environmental factors such as rainfall, larval site characteristics and duration of the dry season. To examine possible physiological divergence between these taxa, we measured metabolic rates of mosquitoes during the wet season in a Sahelian village in Mali. To our knowledge, this study provides the first measurements of metabolic rates of A. gambiae and A. arabiensis in the field. The mean metabolic rate of A. arabiensis was higher than that of M-form A. gambiae when accounting for the effects of female gonotrophic status, temperature and flight activity. However, after accounting for their difference in body size, no significant difference in metabolic rate was found between these two species (whilst all other factors were found to be significant). Thus, body size may be a key character that has diverged in response to ecological differences between these two species. Alternatively, these species may display additional differences in metabolic rate only during the dry season. Overall, our results indicate that changes in behavior and feeding activity provide an effective mechanism for mosquitoes to reduce their metabolic rate, and provide insight into the possible strategies employed by aestivating individuals during the dry season. We hypothesize that female mosquitoes switch to sugar feeding while in dormancy because of elevated metabolism associated with blood digestion.
Hyperbaric computed tomographic measurement of lung compression in seals and dolphins
Authors: Moore Michael John , Hammar Terrence , Arruda Julie , Cramer Scott , Dennison Sophie , Montie Eric , Fahlman Andreas
Published: June 2011

Lung compression of vertebrates as they dive poses anatomical and physiological challenges. There has been little direct observation of this. A harbor and a gray seal, a common dolphin and a harbor porpoise were each imaged post mortem under pressure using a radiolucent, fiberglass, water-filled pressure vessel rated to a depth equivalent of 170 m. The vessel was scanned using computed tomography (CT), and supported by a rail and counterweighted carriage magnetically linked to the CT table movement. As pressure increased, total buoyancy of the animals decreased and lung tissue CT attenuation increased, consistent with compression of air within the lower respiratory tract. Three-dimensional reconstructions of the external surface of the porpoise chest showed a marked contraction of the chest wall. Estimation of the volumes of different body compartments in the head and chest showed static values for all compartments except the lung, which showed a pressure-related compression. The depth of estimated lung compression ranged from 58 m in the gray seal with lungs inflated to 50% total lung capacity (TLC) to 133 m in the harbor porpoise with lungs at 100% TLC. These observations provide evidence for the possible behavior of gas within the chest of a live, diving mammal. The estimated depths of full compression of the lungs exceeds previous indirect estimates of the depth at which gas exchange ceases, and concurs with pulmonary shunt measurements. If these results are representative for living animals, they might suggest a potential for decompression sickness in diving mammals.
Transepitheliald-glucose andd-fructose transport across the American lobster,Homarus americanus, intestine
Authors: Obi Ijeoma E. , Sterling Kenneth M. , Ahearn Gregory A.
Published: June 2011

Transepithelial transport of dietary d-glucose and d-fructose was examined in the lobster Homarus americanus intestine using d-[3H]glucose and d-[3H]fructose. Lobster intestines were mounted in a perfusion chamber to determine transepithelial mucosal to serosal (MS) and serosal to mucosal (SM) transport mechanisms of glucose and fructose. Both MS glucose and fructose transport, as functions of luminal sugar concentration, increased in a hyperbolic manner, suggesting the presence of mucosal transport proteins. Phloridizin inhibited the MS flux of glucose, but not that of fructose, suggesting the presence of a sodium-dependent (SGLT1)-like glucose co-transporter. Immunohistochemical analysis, using a goat anti-rabbit GLUT5 polyclonal antibody, revealed the localization of a brush border GLUT5-like fructose transport protein. MS fructose transport was decreased in the presence of mucosal phloretin in warm spring/summer animals, but the same effect was not observed in cold autumn/winter animals, suggesting a seasonal regulation of sugar transporters. Mucosal phloretin had no effect on MS glucose transport. Both SM glucose and SM fructose transport were decreased in the presence of increasing concentrations of serosal phloretin, providing evidence for the presence of a shared serosal GLUT2 transport protein for the two sugars. The transport of d-glucose and d-fructose across lobster intestine is similar to sugar uptake in mammalian intestine, suggesting evolutionarily conserved absorption processes for these solutes.
Movements ofRana catesbeianatadpoles in weak current flows resemble a directed random walk
Authors: Schmidt Brian P. , Knowles Jeffrey M. , Simmons Andrea Megela
Published: June 2011

Current flow is an important biological stimulus for larval anuran amphibians, but little is known about how it is perceived. We quantified behavioral responses to controlled water flow in the bullfrog tadpole (Rana catesbeiana) at developmental stages prior to metamorphic climax, and examined the contribution of a functioning lateral line system to these behaviors. Tadpoles at these developmental stages show a significant preference for the sides and bottom of a flow tank. In response to water flow at three different rates, they exhibit a significant, time-dependent tendency to move downstream, away from the source of the flow, and to remain in areas where flow is minimized. The consistency of these behaviors at all tested flow rates suggests that the animals are not simply passively pushed by the current; instead, they actively swim away from the current source. Tadpoles do not exhibit positive rheotaxis towards the source of the flow at any flow rate but as a group are randomly oriented. Treatment with cobalt chloride, a known blocker of superficial neuromast function, significantly reduces the tendency to move downstream, but does not alter the preference for the sides and bottom of the tank. Tadpoles' movements under flow are consistent with a model of locomotion based on a directed random walk.
What Determines Productivity?
Authors: Syverson Chad
Published: June 2011

Economists have shown that large and persistent differences in productivity levels across businesses are ubiquitous. This finding has shaped research agendas in a number of fields, including (but not limited to) macroeconomics, industrial organization, labor, and trade. This paper surveys and evaluates recent empirical work addressing the question of why businesses differ in their measured productivity levels. The causes are manifold, and differ depending on the particular setting. They include elements sourced in production practices—and therefore over which producers have some direct control, at least in theory—as well as from producers' external operating environments. After evaluating the current state of knowledge, I lay out what I see are the major questions that research in the area should address going forward. (JEL D24, G31, L11, M10, O30, O47)
Natural Resources: Curse or Blessing?
Authors: Ploeg Frederick van der
Published: June 2011

Are natural resources a “curse” or a “blessing”? The empirical evidence suggests that either outcome is possible. This paper surveys a variety of hypotheses and supporting evidence for why some countries benefit and others lose from the presence of natural resources. These include that a resource bonanza induces appreciation of the real exchange rate, deindustrialization, and bad growth prospects, and that these adverse effects are more severe in volatile countries with bad institutions and lack of rule of law, corruption, presidential democracies, and underdeveloped financial systems. Another hypothesis is that a resource boom reinforces rent grabbing and civil conflict especially if institutions are bad, induces corruption especially in nondemocratic countries, and keeps in place bad policies. Finally, resource rich developing economies seem unable to successfully convert their depleting exhaustible resources into other productive assets. The survey also offers some welfare-based fiscal rules for harnessing resource windfalls in developed and developing economies. (JEL O47, Q32, Q33)
Effects of vibration on the proteome expression of anterior cruciate ligament cells
Authors: Han Gi-Yeon , Park Seung-Ah , Kim Ji-Hye , Lee Eun-Kyung , Kim Hyun-Jung , Seo Young-Kwon , Park Jung-Keug , Kim Chan-Wha
Published: June 2011

Recent reports have suggested that vibration has beneficial effects on knee healing response; however, the biomechanism of these beneficial effects still need to be determined on the anterior cruciate ligament (ACL) cell level. In this study, we applied a 20 Hz vibration to ACL cells, which produced a 20% increase ( P < 0.001) in cell activity and 17% increase ( P < 0.001) in intracellular sulfated glycosaminoglycan levels. In the 20 Hz vibration-stimulated ACL cell group, eight up-regulated (100 ∼ 300%) protein spots were identified compared with the control group by proteomics analysis. Among these proteins, Annexin A2 and Prolyl 4 hydroxylase (PH4B) were shown to have a 71% and 16% higher expression, respectively, in the 20 Hz vibration-stimulated ACL cell group by Western blotting ( P < 0.001). These results indicate that vibration produces a positive cellular environment, and Annexin A2 and prolyl 4 hydroxylase are expected to help ligament repair and ACL cell proliferation by controlling cell membrane and extracellular matrix formation.
Inhibition of eukaryotic translation elongation by the antitumor natural product Mycalamide B
Authors: Dang Yongjun , Schneider-Poetsch Tilman , Eyler Daniel E. , Jewett John C. , Bhat Shridhar , Rawal Viresh H. , Green Rachel , Liu Jun O.
Published: June 2011

Mycalamide B (MycB) is a marine sponge-derived natural product with potent antitumor activity. Although it has been shown to inhibit protein synthesis, the molecular mechanism of action by MycB remains incompletely understood. We verified the inhibition of translation elongation by in vitro HCV IRES dual luciferase assays, ribosome assembly, and in vivo [35S]methinione labeling experiments. Similar to cycloheximide (CHX), MycB inhibits translation elongation through blockade of eEF2-mediated translocation without affecting the eEF1A-mediated loading of tRNA onto the ribosome, AUG recognition, or dipeptide synthesis. Using chemical footprinting, we identified the MycB binding site proximal to the C3993 28S rRNA residue on the large ribosomal subunit. However, there are also subtle, but significant differences in the detailed mechanisms of action of MycB and CHX. First, MycB arrests the ribosome on the mRNA one codon ahead of CHX. Second, MycB specifically blocked tRNA binding to the E-site of the large ribosomal subunit. Moreover, they display different polysome profiles in vivo. Together, these observations shed new light on the mechanism of inhibition of translation elongation by MycB.
microRNAs modulate iPS cell generation
Authors: Yang Chao-Shun , Li Zhonghan , Rana Tariq M.
Published: June 2011

Although induced pluripotent stem cells (iPSCs) hold great promise for customized regenerative medicine, the molecular basis of reprogramming is largely unknown. Overcoming barriers that maintain cell identities is a critical step in the reprogramming of differentiated cells. Since microRNAs (miRNAs) modulate target genes tissue-specifically, we reasoned that distinct mouse embryonic fibroblast (MEF)–enriched miRNAs post-transcriptionally modulate proteins that function as reprogramming barriers. Inhibiting these miRNAs should influence cell signaling to lower those barriers. Here we show that depleting miR-21 and miR-29a enhances reprogramming efficiency in MEFs. We also show that the p53 and ERK1/2 pathways are regulated by miR-21 and miR-29a and function in reprogramming. In addition, we provide the first evidence that c-Myc enhances reprogramming partly by repressing MEF-enriched miRNAs, such as miR-21 and miR-29a. Our results demonstrate the significance of miRNA function in regulating multiple signaling networks involved in iPSC generation. These studies should facilitate development of clinically applicable reprogramming strategies.
Split Rank of Triangle and Quadrilateral Inequalities
Authors: Dey Santanu S. , Louveaux Quentin
Published: June 2011

A simple relaxation consisting of two rows of a simplex tableau is a mixed-integer set with two equations, two free integer variables, and nonnegative continuous variables. Recently, Andersen et al. and Cornuéjols and Margot showed that the facet-defining inequalities of this set are either split cuts or intersection cuts obtained from lattice-free triangles and quadrilaterals. From an example given by Cook et al. it is known that one particular class of facet-defining triangle inequality does not have finite split rank. In this paper we show that all other facet-defining triangle and quadrilateral inequalities have finite split rank.
Dihydroergotamine-Induced Vasospastic Angina in a Patient Taking a Calcium Channel Blocker
Authors: Schenkat Daniel H , Schulz Lucas T , Johnson Benjamin D
Published: June 2011

Objective:

To report a probable case of vasospastic angina after administration of dihydroergotamine mesylate in a patient without coronary artery disease.

Case Summary:

A 49-year-old woman with relapsing/remitting multiple sclerosis was admitted for severe headache and pain crisis. She received a single dose of intravenous dihydroergotamine and, within 30 minutes, experienced chest pain, nausea, and vomiting. No changes on electrocardiogram were noted, but cardiac enzyme levels were elevated. Brief episodes of chest pain persisted for several days and resolved spontaneously before the woman's discharge. She had several cardiac risk factors, including cigarette smoking, hypertension, and a family history of coronary artery disease, but cardiac catheterization on hospital day 5 revealed no underlying coronary artery disease.

Discussion:

Although cardiovascular adverse reactions have been reported with ergotamine tartrate, dihydroergotamine has rarely been linked with such reactions, including coronary vasospasm and myocardial infarction. Prescribing information for dihydroergotamine cautions against its use in patients with coronary artery disease or risk factors for underlying coronary artery disease without a cardiac workup before initiation of therapy. This patient had several cardiac risk factors, but cardiac catheterization revealed no underlying coronary artery disease. Concomitant verapamil therapy for hypertension did not prevent the vasospastic effects of dihydroergotamine. The Naranjo probability scale revealed a probable adverse reaction of vasospastic angina associated with dihydroergotamine.

Conclusions:

Health-care professionals should be aware of the possibility for vasospastic angina in patients receiving dihydroergotamine who have no underlying coronary artery disease. Prescribing information should be closely followed.
Oxidized LDL and the Risk of Coronary Heart Disease: Results from the MONICA/KORA Augsburg Study
Authors: Koenig Wolfgang , Karakas Mahir , Zierer Astrid , Herder Christian , Baumert Jens , Meisinger Christa , Thorand Barbara
Published: June 2011

BACKGROUND

Oxidative stress plays a critical role in the initiation and progression of atherosclerosis. Oxidized LDL (oxLDL) is a marker of oxidative stress. We prospectively investigated whether increased serum oxLDL concentrations are associated with incident coronary heart disease (CHD).

METHODS

We conducted a prospective population-based case–cohort study within the MONICA/KORA Augsburg studies. Serum oxLDL concentrations were measured in 333 case individuals with incident CHD and in 1727 noncase individuals selected from a source population of 9300 middle-aged, healthy men and women. The mean (SD) follow-up time was 10.8 (4.6) years.

RESULTS

Baseline oxLDL concentrations were higher in case individuals than in noncase individuals (P < 0.001). After adjustment for age, sex, survey, smoking status, systolic blood pressure, physical activity, diabetes, body mass index, parental history of myocardial infarction, and alcohol consumption, the hazard ratio (HR) for comparing the first and third tertiles was 1.87 (95% CI, 1.33–2.64; P < 0.001). Additional adjustment for lipid parameters, inflammatory markers, and markers of endothelial dysfunction attenuated the association (HR, 1.29; 95% CI, 0.88–1.89; P = 0.087). We observed no significant interactions between oxLDL and sex or being overweight.

CONCLUSIONS

Increased oxLDL concentrations were associated with an increased risk for incident CHD. Nevertheless, because this effect became nonsignificant after adjustment for covariates, particularly the ratio of total cholesterol to HDL cholesterol, it may be mediated primarily by lipid parameters. Further studies are warranted to clarify this issue.
The value of N-terminal proB-type natriuretic peptide for early identification of myocardial infarction in patients with high-risk non-ST-elevation acute coronary syndromes
Authors: Riezebos Robert K. , Laarman Gerrit J. , Tijssen Jan G.P. , Verheugt Freek W.A.
Published: June 2011

Background: N-terminal proB-type natriuretic peptide (NT-proBNP) is a marker of biomechanical strain, secreted by cardiomyocytes in response to ischemia. As necrosis occurs after prolonged ischemia, a rise in NT-proBNP concentration could precede a rise in markers of necrosis.

Methods: The aim of the study was to evaluate whether NT-proBNP is able to identify those patients with an evolving myocardial infarction (MI) with high-risk non-ST-elevation acute coronary syndromes (NSTE-ACS). Data were analyzed from a prospective cohort of 103 high-risk NSTE-ACS patients admitted within 6 h after onset of pain and treated with an early invasive strategy. NT-proBNP samples, obtained immediately upon admission, were related to the presence of an in hospital MI. The optimal cut-off value for NT-proBNP was determined using receiver-operating characteristics (ROC) curve analysis.

Results: Analyses was performed separately for creatinine kinase MB-mass (CKMB) and troponin T (TnT) based MI definitions. In both cases, a NT-proBNP concentration above 40 pmol/L (339 ng/L) at admission proved to be independently associated with the presence of MI. The diagnostic odds ratio (OR) for CKMB-MI was 4.9 (confidence interval 2.0–11.9, p<0.001). The diagnostic OR for TnT-MI was 4.9 (1.8–14.4, p=0.003). Adjusting for differences in baseline variables did not weaken the diagnostic OR. In addition, elevated NT-proBNP concentrations were related to unfavour-able demographic, physical and biochemical parameters.

Conclusions: With a dichotomous cut-off value, a single elevated NT-proBNP (>40 pmol/L) at admission provides independent information about the presence of MI in high-risk NSTE-ACS patients.
Time and the Keyboard Fugue
Authors: Chapin Keith
Published: June 2011

Throughout the history of Western music, musicians have almost invariably discussed the keyboard fugue and other extreme forms of polyphony as signs of something that transcends human subjectivity. Despite the persistence of this critical topos, musicians shifted their approach to it around the beginning of the nineteenth century. The shift involved both a change in the technique of counterpoint and a change in the way counterpoint was interpreted. Composers sought to invest the fugue with a new dramatic and teleological thrust suitable to modern times, and critically minded musicians changed their interpretive method so as to emphasize the passage of time. Whereas musicians of the early eighteenth century read counterpoint and the fugue allegorically and annulled time through the conceptual precision of the allegorical image, musicians of the late eighteenth and early nineteenth centuries read the fugue symbolically and worked time into their interpretive process. In both eras, the practice of interpretation coincided with and affected the reading of the genre's temporality.
P nutrient status of maize and the phosphorus–zinc interaction in a long-term mineral fertilization experiment on chernozem meadow soil
Authors: Izsáki Zoltán
Published: June 2011

Kukorica műtrágyázási tartamkísérletben vizsgáltuk a talaj P-ellátottságának hatását a kukorica szemtermésére, P- és Zn-tápláltsági állapotára, valamint e két tápelem kölcsönhatására.
A műtrágyázási tartamkísérletet 1989-ben állítottuk be mélyben karbonátos csernozjom réti talajon, 4–4 N-, P- és K-ellátottsági szinten, teljes kezelés-kombinációban, 64 kezeléssel. A talaj főbb jellemzői: a humuszos réteg vastagsága 85–100 cm, humusztartalom 2,8–3,2%, a művelt réteg pH(KCl)-ja 5,0-5,2, kötöttsége (KA) 50, agyagtartalma 32%, az AL-P2O5-tartalma a P-trágyázástól függően 120–362 mg·kg-1, EDTA Zn-tartalma 3,0 mg·kg-1.
Jelen dolgozatban a 2001 és 2008 között, a tartamkísérlet 12–19. éveiben végzett kísérletek P-trágyázási eredményei szerepelnek, melyek alapján az alábbi főbb következtetések tehetők:
– A savanyú kémhatású agyagos vályogtalajon, melynek P-ellátottsága P-trágyázás nélkül 120–150 mg AL-P2O5·kg-1 között változott, a kukorica szemtermése 7,39 t·ha-1 volt a nyolc év átlagában. A szemtermés maximuma a 160–220 mg AL-P2O5·kg-1 ellátottsági szinten jelentkezett. Ennél magasabb P-ellátottságnál (360 mg AL-P2O5·kg-1 értékig), a terméshozamban érdemi változás nem volt kimutatható.
– A címerhányás kezdetén végzett levélanalízis eredményei szerint a jobb P-ellátottságot a kukoricalevél nagyobb P-koncentrációja kísérte. A kukoricalevél P-koncentrációja és a szemtermés közötti összefüggés-vizsgálatok alapján meghatározott kielégítő P-ellátottsági határérték a 10–14 t·ha-1 szemtermésszinten a 0,20–0,37% P-koncentrációhoz kötődik.
– A növekvő P-ellátottságot kísérő P–Zn antagonizmus a 160 mg AL-P2O5·kg-1 ellátottsági szinttől érvényesült, de a 160–360 mg AL-P2O5·kg-1 ellátottsági tartományban és a művelt réteg kielégítő Zn-ellátottságánál a kukorica Zn-tápláltságá-nak csökkenése termésdepressziót nem váltott ki.
– A kukoricalevél Zn-koncentrációja, P/Zn aránya és a szemtermés közötti összefüggés-vizsgálatok alapján a 10–14 t·ha-1 termésszinthez tartozó kielégítő Zn-koncentráció 10–32 mg Zn·kg-1, a P/Zn arány pedig 80–330.