bluuebunny/crossref_metadata_2025 huggingface dataset:
Mid-wave infrared HgCdTe nBn photodetector
Authors: Itsuno Anne M. , Phillips Jamie D. , Velicu Silviu
Published: April 2012

A unipolar, barrier-integrated HgCdTe nBn photodetector with all n-type doping and a type-I band lineup is experimentally demonstrated. Planar mid-wave infrared (MWIR) nBn devices exhibit current-voltage (I-V) characteristics that are consistent with band inversion in reverse bias, indicating a barrier-influenced behavior. Dark current saturation is observed beyond a reverse bias of approximately −0.8 V. Bias-dependent photoresponse is observed in the mid-wave infrared with a cut-off wavelength around 5.7 μm. Numerical modeling based on experimental results predicts an internal peak quantum efficiency of approximately 66%.
Opto-electric particle manipulation on a bismuth silicon oxide crystal
Authors: Esseling Michael , Glasener Stefan , Volonteri Federico , Denz Cornelia
Published: April 2012

High-throughput manipulation of microparticles can be efficiently accomplished using electrokinetic effects. In this contribution, we demonstrate the two-dimensional investigation of internal space-charge fields inside a bismuth silicon oxide (BSO) crystal and their use for optically mediated particle trapping. The magnitude of the internal fields as well as the time constant for its build-up are measured by Zernike phase contrast and digital holography. The fast response time of a BSO crystal at very low light powers enables real-time generation of high electric field gradients. We demonstrate that this photoconductive material facilitates both electrophoretic and dielectrophoretic trapping of particles on an accessible surface.
Note: Characterization of CaF2/acetone bandpass photon detector with Kr filter gas
Authors: Maniraj M. , Sekhar B. N. Raja , Barman S. R.
Published: April 2012

A modified design of a CaF2/acetone bandpass photon detector that uses Kr as a filter gas to tune the energy resolution is presented. Our design combines two standard single window detector tubes to build the Kr filter gas chamber. Synchrotron radiation has been used to determine the energy resolution of the detector, as a function of Kr pressure. The improvement in the detector energy resolution by 250 meV compared to the CaF2/acetone detector is better than that reported earlier. Substantial variation in the shape of the CaF2/acetone detector response functions is observed for different acetone pressure (≤3 mbar), and anode voltage (≤800 V). Our analysis reveals that the changes in the shape of the detector response function are associated to different regions of the detector operation.
Note: Real time control of a tunable vibration absorber based on magnetorheological elastomer for suppressing tonal vibrations
Authors: Kim Young-Keun , Bae Hyo-In , Koo Jeong-Hoi , Kim Kyung-Soo , Kim Soohyun
Published: April 2012

An adaptive tunable vibration absober based on magnetorheological elastomer (MRE) is designed as an intelligent device for auto-tuning itself to the time-varying harmonic disturbance force to reduce the unwanted vibration of the primary system in the steady state. The objectives of this note are to develop and implement a continuous control method for a MRE tunable vibration absorber (TVA) and to evaluate its performance in suppressing time-varying tonal vibrations. In the proposed control, the stiffness of MREs is continuously varied based on a nonlinear tuning function that relates the response of the system to the input magnetic field density. Through experiments, it will be shown that the proposed MRE TVA reduces in real time the transmission of a time-varying excited vibration of 48–55 Hz, which shows the potential applicability of the MRE in reducing unwanted vibration to precision devices.
Magnetoresistance and its relation to magnetization in Ni50Mn35Sn15 shape-memory epitaxial films
Authors: Dubowik J. , Załȩski K. , Gościańska I. , Głowiński H. , Ehresmann A.
Published: April 2012

The magnetoresistance (MR) of Heusler alloy Ni50Mn35Sn15 epitaxial films on MgO substrates is studied as a function of temperature T and magnetic field H. The large negative MR extends over martensitic transformation with maximum of −22% at 110 K. In martensitic and austenitic phase, the MR is −3% and −5%, respectively. We show that the MR is governed mainly by magnetization paraprocess at high magnetic fields and scales as the square of magnetization Δm(H,T)2.
Critical dimensions of highly lattice mismatched semiconductor nanowires grown in strain-releasing configurations
Authors: Sburlan Suzana , Daniel Dapkus P. , Nakano Aiichiro
Published: April 2012

Growing large defect-free semiconductor nanowires (NW) on lattice-mismatched substrates is important for solar cell applications. Here, we evaluate the critical dimensions of NWs in several strain-releasing growth configurations of interest to experimentalists. We quantify the expected increase in NW volume that may be grown coherently for NWs stacked on lattice mismatched pillars and embedded quantum dot (QD) layers, compared to NWs grown on simple substrates. We also calculate the variations in strain energy for NWs positioned off-axis from embedded QDs, as may occur during fabrication. We predict significant increases in coherent NW volume allowing greater absorption efficiency in solar cells.
Unusual photoresponse of indium doped ZnO/organic thin film heterojunction
Authors: Vempati Sesha , Chirakkara Saraswathi , Mitra J. , Dawson Paul , Kar Nanda Karuna , Krupanidhi S. B.
Published: April 2012

Photoresponse of n-type indium-doped ZnO and a p-type polymer (PEDOT:PSS) heterojunction devices are studied, juxtaposed with the photoluminescence of the In-ZnO samples. In addition to the expected photoresponse in the ultraviolet, the heterojunctions exhibit significant photoresponse to the visible (532 nm). However, neither the doped ZnO nor PEDOT:PSS individually show any photoresponse to visible light. The sub-bandgap photoresponse of the heterojunction originates from visible photon mediated e-h generation between the In-ZnO valence band and localized states lying within the band gap. Though increased doping of In-ZnO has limited effect on the photoluminescence, it significantly diminishes the photoresponse. The study indicates that optimally doped devices are promising for the detection of wavelengths in selected windows in the visible.
Magnetoexcitons and optical absorption of bilayer-structured topological insulators
Authors: Wang Zhigang , Fu Zhen-Guo , Zhang Ping
Published: April 2012

The optical absorption properties of magnetoexcitons in topological insulator bilayers under a strong magnetic field are theoretically studied. A general analytical formula of optical absorption selection rule is obtained in the noninteracting as well as Coulomb intra-Landau-level (LL) interacting cases, which remarkably helps to interpret the resonant peaks in absorption spectroscopy and the corresponding formation of Dirac-type magnetoexcitons. We also discuss the optical absorption spectroscopy of magnetoexcitons in the presence of inter-Landau-level Coulomb interaction, which becomes more complex. We hope our results can be detected in the future magneto-optical experiments.
Composition dependent bilayer atomic ordering in AlxGa1−xN films examined by polarization-dependent extended x-ray absorption fine structure
Authors: Woicik J. C. , Ludwig K. F. , Moustakas T. D.
Published: April 2012

Extended x-ray absorption fine structure has been used to study the local structure of ordered AlxGa1−xN films with nominal concentrations of x = 0.20 and x = 0.45. Strong cation ordering is found in alternating (0001) planes for both samples, with the 20% sample exhibiting nearly ideal local order compared to the 45% sample. Significant distortions in the nearest-neighbor Ga-N distances compared to the virtual crystal approximation are observed, although these distortions are found to be smaller than for disordered films. This result is counter to current theoretical predictions.
Electrically controllable energy gaps in graphene quantum dots
Authors: Ma Wen-Long , Li Shu-Shen
Published: April 2012

We theoretically demonstrate that the energy gaps of graphene quantum dots (GQDs) can be easily tuned by applying opposite electrostatic potentials to the two equally divided parts of them. This control of energy gaps by such an external electrostatic potential can be realized in various sizes or shapes of GQDs. We propose that the physical origin of the gap tunability is the delicate coupling between the two parts of GQDs with opposite electrostatic gate potentials. Our findings are quite useful for the application of GQDs to the electronic devices and photovoltaic devices.
Dynamic nanomechanics of zinc oxide nanowires
Authors: Wang Lifen , Tian Xuezeng , Yang Shize , Xu Zhi , Wang Wenlong , Bai Xuedong
Published: April 2012

The electromechanical resonances of individual zinc oxide nanowires were induced by alternative current (ac) signals inside a transmission electron micrcrope, which have been used to measure the mechanical quality factors (Q) and elastic bending moduli (E) of a single zinc oxide (ZnO) nanowire. The resonance amplitudes were tuned by the applied ac voltages. The results indicate that Q drops as much as ∼80% with increasing resonance amplitudes, while E slightly decreases (∼3%). The mechanism of the amplitude-dependent mechanical properties is discussed. This study on dynamic nanomechanics of ZnO nanowires is significant for their cantilever-based applications.
DNA-decorated carbon nanotube-based FETs as ultrasensitive chemical sensors: Discrimination of homologues, structural isomers, and optical isomers
Authors: Khamis S. M. , Jones R. A. , Johnson A. T. C. , Preti G. , Kwak J. , Gelperin A.
Published: April 2012

We have explored the abilities of all-electronic DNA-carbon nanotube (DNA-NT) vapor sensors to discriminate very similar classes of molecules. We screened hundreds of DNA-NT devices against a panel of compounds chosen because of their similarities. We demonstrated that DNA-NT vapor sensors readily discriminate between series of chemical homologues that differ by single methyl groups. DNA-NT devices also discriminate among structural isomers and optical isomers, a trait common in biological olfactory systems, but only recently demonstrated for electronic FET based chemical sensors.
Lateral energy band profile modulation in tunnel field effect transistors based on gate structure engineering
Authors: Cui Ning , Liang Renrong , Wang Jing , Xu Jun
Published: April 2012

Choosing novel materials and structures is important for enhancing the on-state current in tunnel field-effect transistors (TFETs). In this paper, we reveal that the on-state performance of TFETs is mainly determined by the energy band profile of the channel. According to this interpretation, we present a new concept of energy band profile modulation (BPM) achieved with gate structure engineering. It is believed that this approach can be used to suppress the ambipolar effect. Based on this method, a Si TFET device with a symmetrical tri-material-gate (TMG) structure is proposed. Two-dimensional numerical simulations demonstrated that the special band profile in this device can boost on-state performance, and it also suppresses the off-state current induced by the ambipolar effect. These unique advantages are maintained over a wide range of gate lengths and supply voltages. The BPM concept can serve as a guideline for improving the performance of nanoscale TFET devices.
Development of a versatile capacitive tactile sensor based on transparent flexible materials integrating an excellent sensitivity and a high resolution
Authors: Zhang H. Z. , Tang Q. Y. , Chan Y. C.
Published: April 2012

A versatile capacitive tactile sensor based on transparent flexible materials is developed in a simple and low-cost fabrication process. The sensor shows an excellent sensitivity (S=2.05 N-1), and is highly sensitive to the load as low as about 3 mN. Moreover, it exhibits a prominent resolution. The excellent device performance is attributed to the creative design of polydimethylsiloxane (PDMS) polymer layer, used as the structural material of the sensor, in which each sensing section acting as a sensor unit is a concave square with hemispheric micro-structured PDMS arrays. Meanwhile, other sections without any PDMS arrays serving as perfect natural wall-barriers can make each sensor unit separated effectively.
Arbuscular mycorrhizal fungi improve the growth and nodulation of the annual legume messina (Melilotus siculus) under saline and non-saline conditions
Authors: Wilson B. A. L. , Ash G. J. , Harper J. D. I.
Published: April 2012

Messina [Melilotus siculus (Turra) Vitman ex. B. D Jacks] is a salt- and waterlogging-tolerant annual legume that could be highly productive on saline land. Arbuscular mycorrhizal (AM) fungi form a symbiotic relationship with the majority of terrestrial plant species, and improved productivity of plants inoculated with AM fungi under saline conditions has been attributed to the increased uptake of nutrients such as phosphorus (P). However, the mycorrhizal status of M. siculus under saline or non-saline conditions is unknown, as is the role of AM in improved nutrition and nodulation. In this study, the role of AM fungi in growth improvement and nodulation of M. siculus was examined in saline and non-saline soil. The M. siculus plants were inoculated with either a single AM species or mixed AM species, or remained uninoculated, and were grown at three levels of sodium chloride (NaCl) (0, 80, and 250 mm NaCl). AM-inoculated plants had significantly greater nodulation than plants that did not receive AM inoculum, regardless of salinity level. Plants inoculated with mixed AM species at 250 mm NaCl showed improved survival (90%) compared with the plants inoculated with single AM species or uninoculated control plants (30%). Within each salinity level, plants inoculated with mixed AM species had significantly greater dry weight than all other treatments. In addition, plants inoculated with mixed AM species had increased total uptake of P. It is likely that the increased growth observed in AM-inoculated M. siculus plants is due to improved P nutrition, showing the potential of AM fungi to enhance the growth of M. siculus on saline land.
Adaptation analysis of diversity in adzuki germplasm introduced into Australia
Authors: Redden R. J. , Kroonenberg P. M. , Basford K. E.
Published: April 2012

Adzuki bean germplasm was introduced to Australia from China as part of a program to develop better adapted varieties for the Australian sub-tropics than the current standard varieties derived from Japan, and to develop an export industry targeting Japan. Since adzuki was a new crop in Australia, the key questions were whether suitably adapted genotypes could be obtained from China, and whether these were higher yielding than the Japanese derived local standards and of acceptable seed quality.
A geographically stratified core collection of adzuki bean (Vigna angularis) landraces from China was field evaluated for agronomic and phenologic traits at sites in China in a related study, and also at Hermitage Research Station, Queensland, in the main target region for adzuki cultivation in Australia.
A relationship was found between the regional patterns of adaptation in the core collection grown in China and yield performance at Hermitage. In particular, the late maturing gene pool which originated from South China had the greatest yield at the lower latitude location in Australia, and a gene pool from central China combined both high yield and acceptable seed quality. These lines from China were superior in yield to the local standards, and many also had suitable seed quality for the Japanese market.
In further screening of these selections from Hermitage, they were also superior in yield to the local standards in central Queensland, but not in central New South Wales.
The breeding of higher yielding varieties for Queensland with suitable quality for the Japanese market is suggested, both by direct releases of identified Chinese accessions and by further crossing of the medium and late maturing superior selections from China with the local standard varieties Erimo and Bloodwood, which have the large red seed desired in Japan.
For New South Wales, one accession from China was comparable to the local checks and appears useful for gene pool diversification, however a separate introductory screening evaluation of Chinese germplasm in New South Wales is suggested to better identify promising accessions with phenology suited to the more temperate latitudes.
Thus characterisation of genetic diversity for adaptation can assist with the introduction of germplasm for a new crop. The diversity in the adzuki germplasm from China provided the needed phenologic flexibility for introduction of the crop to southern Queensland, with superior yield to the standard varieties from Japan and acceptable seed quality.
Dynamic reciprocity of sodium and potassium channel expression in a macromolecular complex controls cardiac excitability and arrhythmia
Authors: Milstein Michelle L. , Musa Hassan , Balbuena Daniela Ponce , Anumonwo Justus M. B. , Auerbach David S. , Furspan Philip B. , Hou Luqia , Hu Bin , Schumacher Sarah M. , Vaidyanathan Ravi , Martens Jeffrey R. , Jalife José
Published: April 2012

The cardiac electrical impulse depends on an orchestrated interplay of transmembrane ionic currents in myocardial cells. Two critical ionic current mechanisms are the inwardly rectifying potassium current (I
K1
), which is important for maintenance of the cell resting membrane potential, and the sodium current (I
Na
), which provides a rapid depolarizing current during the upstroke of the action potential. By controlling the resting membrane potential, I
K1
modifies sodium channel availability and therefore, cell excitability, action potential duration, and velocity of impulse propagation. Additionally, I
K1
–I
Na
interactions are key determinants of electrical rotor frequency responsible for abnormal, often lethal, cardiac reentrant activity. Here, we have used a multidisciplinary approach based on molecular and biochemical techniques, acute gene transfer or silencing, and electrophysiology to show that I
K1
–I
Na
interactions involve a reciprocal modulation of expression of their respective channel proteins (Kir2.1 and Na
V
1.5) within a macromolecular complex. Thus, an increase in functional expression of one channel reciprocally modulates the other to enhance cardiac excitability. The modulation is model-independent; it is demonstrable in myocytes isolated from mouse and rat hearts and with transgenic and adenoviral-mediated overexpression/silencing. We also show that the
p
ost synaptic density,
d
iscs large, and
z
onula occludens-1 (PDZ) domain protein SAP97 is a component of this macromolecular complex. We show that the interplay between Na
v
1.5 and Kir2.1 has electrophysiological consequences on the myocardium and that SAP97 may affect the integrity of this complex or the nature of Na
v
1.5–Kir2.1 interactions. The reciprocal modulation between Na
v
1.5 and Kir2.1 and the respective ionic currents should be important in the ability of the heart to undergo self-sustaining cardiac rhythm disturbances.
Representation of stable social dominance relations by human infants
Authors: Mascaro Olivier , Csibra Gergely
Published: April 2012

What are the origins of humans’ capacity to represent social relations? We approached this question by studying human infants’ understanding of social dominance as a stable relation. We presented infants with interactions between animated agents in conflict situations. Studies 1 and 2 targeted expectations of stability of social dominance. They revealed that 15-mo-olds (and, to a lesser extent, 12-mo-olds) expect an asymmetric relationship between two agents to remain stable from one conflict to another. To do so, infants need to infer that one of the agents (the dominant) will consistently prevail when her goals conflict with those of the other (the subordinate). Study 3 and 4 targeted the format of infants’ representation of social dominance. In these studies, we found that 12- and 15-mo-olds did not extend their expectations of dominance to unobserved relationships, even when they could have been established by transitive inference. These results suggest that infants' expectation of stability originates from their representation of social dominance as a relationship between two agents rather than as an individual property. Infants’ demonstrated understanding of social dominance reflects the cognitive underpinning of humans’ capacity to represent social relations, which may be evolutionarily ancient, and may be shared with nonhuman species.
On the origin of the hierarchy of color names
Authors: Loreto Vittorio , Mukherjee Animesh , Tria Francesca
Published: April 2012

One of the fundamental problems in cognitive science is how humans categorize the visible color spectrum. The empirical evidence of the existence of universal or recurrent patterns in color naming across cultures is paralleled by the observation that color names begin to be used by individual cultures in a relatively fixed order. The origin of this hierarchy is largely unexplained. Here we resort to multiagent simulations, where a population of individuals, subject to a simple perceptual constraint shared by all humans, namely the human Just Noticeable Difference, categorizes and names colors through a purely cultural negotiation in the form of language games. We found that the time needed for a population to reach consensus on a color name depends on the region of the visible color spectrum. If color spectrum regions are ranked according to this criterion, a hierarchy with [red, (magenta)-red], [violet], [green/yellow], [blue], [orange], and [cyan], appearing in this order, is recovered, featuring an excellent quantitative agreement with the empirical observations of the WCS. Our results demonstrate a clear possible route to the emergence of hierarchical color categories, confirming that the theoretical modeling in this area has now attained the required maturity to make significant contributions to the ongoing debates concerning language universals.
The expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia
Authors: Kang Rui , Loux Tara , Tang Daolin , Schapiro Nicole E. , Vernon Philip , Livesey Kristen M. , Krasinskas Alyssa , Lotze Michael T. , Zeh Herbert J.
Published: April 2012

Pancreatic cancer is an almost uniformly lethal disease, characterized by late diagnosis, early metastasis, resistance to chemotherapy, and early mutation of theKrasoncogene. Here we show that the receptor for advanced glycation endproducts (RAGE) is required for the activation of interleukin 6 (IL-6)–mediated mitochondrial signal transducers and activators of transcription 3 (STAT3) signaling in pancreatic carcinogenesis. RAGE expression correlates with elevated levels of autophagy in pancreatic cancer in vivo and in vitro, and this heightened state of autophagy is required for IL-6–induced STAT3 activation. To further explore the intersection of RAGE, autophagy, and pancreatic carcinogenesis, we created a transgenic murine model, backcrossing RAGE-null mice to a spontaneous mouse model of pancreatic cancer,Pdx1-Cre:KrasG12D/+(KC). Targeted ablation ofRagein KC mice delayed neoplasia development, decreased levels of autophagy, and inhibited mitochondrial STAT3 activity and subsequent ATP production. Our results suggest a critical role for RAGE expression in the earliest stages of pancreatic carcinogenesis, potentially acting as the “autophagic switch,” regulating mitochondrial STAT3 signaling.
Atomic structure of the autosomal recessive hypercholesterolemia phosphotyrosine-binding domain in complex with the LDL-receptor tail
Authors: Dvir Hay , Shah Mehul , Girardi Enrico , Guo Lixia , Farquhar Marilyn G. , Zajonc Dirk M.
Published: April 2012

Hypercholesterolemia, high serum cholesterol in the form of LDL, is a major risk factor for atherosclerosis. LDL is mostly degraded in the liver after its cellular internalization with the LDL receptor (LDLR). This clathrin-mediated endocytosis depends on the protein autosomal recessive hypercholesterolemia (ARH), which binds the LDLR cytoplasmic tail. Mutations in either the LDLR tail or in ARH lead to hypercholesterolemia and premature atherosclerosis. Despite the significance of this interaction for cholesterol homeostasis, no structure of either ARH or the LDLR tail is available to determine its molecular basis. We report the crystal structure at 1.37-Å resolution of the phosphotyrosine-binding (PTB) domain of ARH in complex with an LDLR tail peptide containing the FxNPxY
0
internalization signal. Surprisingly, ARH interacts with a longer portion of the tail than previously recognized, which extends to I
-7
xF
-5
xNPxY
0
QK
+2
. The LDLR tail assumes a unique “Hook”-like structure with a double β-turn conformation, which is accommodated in distinctive ARH structural determinants (i.e., an extended backbone hydrogen-bonding platform, three hydrophobic helical grooves, and a hydrophobic pocket for Y
0
). This unique complementarity differs significantly in related PTB proteins and may account for the unique physiological role of these partners in the hepatic uptake of cholesterol LDL. Moreover, the unusual hydrophobic pocket for Y
0
explains the distinctive ability of ARH to internalize proteins containing either FxNPxY
0
or FxNPxF
0
sequences. Biophysical measurements reveal how mutations associated with hypercholesterolemia destabilize ARH and its complex with LDLR and illuminate LDL internalization defects seen in patients.
Agulhas leakage as a key process in the modes of Quaternary climate changes
Authors: Caley Thibaut , Giraudeau Jacques , Malaizé Bruno , Rossignol Linda , Pierre Catherine
Published: April 2012

Heat and salt transfer from the Indian Ocean to the Atlantic Ocean (Agulhas leakage) has an important effect on the global thermohaline circulation and climate. The lack of long transfer record prevents elucidation of its role on climate changes throughout the Quaternary. Here, we present a 1,350-ka accumulation rate record of the planktic foraminiferal species
Globorotalia menardii
. We demonstrate that, according to previous assumptions, the presence and reseeding of this fauna in the subtropical southeast Atlantic was driven by interocean exchange south of Africa. The Agulhas transfer strengthened at glacial ice-volume maxima for every glacial-interglacial transition, with maximum reinforcements organized according to a 400-ka periodicity. The long-term dynamics of Agulhas leakage may have played a crucial role in regulating meridional overturning circulation and global climate changes during the Mid-Brunhes event and the Mid-Pleistocene transition, and could also play an important role in the near future.
Langerhans cells down-regulate inflammation-driven alveolar bone loss
Authors: Arizon Moran , Nudel Itay , Segev Hadas , Mizraji Gabriel , Elnekave Mazal , Furmanov Karina , Eli-Berchoer Luba , Clausen Björn E. , Shapira Lior , Wilensky Asaf , Hovav Avi-Hai
Published: April 2012

Excessive bone resorption is frequently associated with chronic infections and inflammatory diseases. Whereas T cells were demonstrated to facilitate osteoclastogenesis in such diseases, the role of dendritic cells, the most potent activators of naive T cells, remains unclear. Using a model involving inflammation-driven alveolar bone loss attributable to infection, we showed that in vivo ablation of Langerhans cells (LCs) resulted in enhanced bone loss. An increased infiltration of B and T lymphocytes into the tissue surrounding the bone was observed in LC-ablated mice, including receptor activator of NF-κB ligand (RANKL)-expressing CD4+T cells with known capabilities of altering bone homeostasis. In addition, the absence of LCs significantly reduced the numbers of CD4+Foxp3+T-regulatory cells in the tissue. Further investigation revealed that LCs were not directly involved in presenting antigens to T cells. Nevertheless, despite their low numbers in the tissue, the absence of LCs resulted in an elevated activation of CD4+but not CD8+T cells. This activation involved elevated production of IFN-γ but not IL-17 or IL-10 cytokines. Our data, thus, reveal a protective immunoregulatory role for LCs in inflammation-induced alveolar bone resorption, by inhibiting IFN-γ secretion and excessive activation of RANKL+CD4+T cells with a capability of promoting osteoclastogenesis.
Amorfrutins are potent antidiabetic dietary natural products
Authors: Weidner Christopher , de Groot Jens C. , Prasad Aman , Freiwald Anja , Quedenau Claudia , Kliem Magdalena , Witzke Annabell , Kodelja Vitam , Han Chung-Ting , Giegold Sascha , Baumann Matthias , Klebl Bert , Siems Karsten , Müller-Kuhrt Lutz , Schürmann Annette , Schüler Rita , Pfeiffer Andreas F. H. , Schroeder Frank C. , Büssow Konrad , Sauer Sascha
Published: April 2012

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes,
Glycyrrhiza foetida
and
Amorpha fruticosa
, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.
Tempo of trophic evolution and its impact on mammalian diversification
Authors: Price Samantha A. , Hopkins Samantha S. B. , Smith Kathleen K. , Roth V. Louise
Published: April 2012

Mammals are characterized by the complex adaptations of their dentition, which are an indication that diet has played a critical role in their evolutionary history. Although much attention has focused on diet and the adaptations of specific taxa, the role of diet in large-scale diversification patterns remains unresolved. Contradictory hypotheses have been proposed, making prediction of the expected relationship difficult. We show that net diversification rate (the cumulative effect of speciation and extinction), differs significantly among living mammals, depending upon trophic strategy. Herbivores diversify fastest, carnivores are intermediate, and omnivores are slowest. The tempo of transitions between the trophic strategies is also highly biased: the fastest rates occur into omnivory from herbivory and carnivory and the lowest transition rates are between herbivory and carnivory. Extant herbivore and carnivore diversity arose primarily through diversification within lineages, whereas omnivore diversity evolved by transitions into the strategy. The ability to specialize and subdivide the trophic niche allowed herbivores and carnivores to evolve greater diversity than omnivores.
Selective recruitment of G protein-coupled receptor kinases (GRKs) controls signaling of the insulin-like growth factor 1 receptor
Authors: Zheng Huiyuan , Worrall Claire , Shen Hongchang , Issad Tarik , Seregard Stefan , Girnita Ada , Girnita Leonard
Published: April 2012

β-Arrestins are multifunctional proteins that play central roles in G protein-coupled receptor (GPCR) trafficking and signaling. β-Arrestin1 is also recruited to the insulin-like growth factor-1 receptor (IGF-1R), a receptor tyrosine kinase (RTK), mediating receptor degradation and signaling. Because GPCR phosphorylation by GPCR-kinases (GRKs) governs interactions of the receptors with β-arrestins, we investigated the regulatory roles of the four widely expressed GRKs on IGF-1R signaling/degradation. By suppressing GRK expression with siRNA, we demonstrated that lowering GRK5/6 abolishes IGF1-mediated ERK and AKT activation, whereas GRK2 inhibition increases ERK activation and partially inhibits AKT signaling. Conversely, β-arrestin–mediated ERK signaling is enhanced by overexpression of GRK6 and diminished by GRK2. Similarly, we demonstrated opposing effects of GRK2 and -6 on IGF-1R degradation: GRK2 decreases whereas GRK6 enhances ligand-induced degradation. GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R, and subsequent mutation analysis demonstrated clear effects on IGF-1R signaling and degradation, mirroring alterations by GRKs. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation, consistent with GRK isoform-specific serine phosphorylation. This study demonstrates distinct roles for GRK isoforms in IGF-1R signaling through β-arrestin binding with divergent functional outcomes.
Differentiation of vascular smooth muscle cells from local precursors during embryonic and adult arteriogenesis requires Notch signaling
Authors: Chang Linda , Noseda Michela , Higginson Michelle , Ly Michelle , Patenaude Alexandre , Fuller Megan , Kyle Alastair H. , Minchinton Andrew I. , Puri Mira C. , Dumont Daniel J. , Karsan Aly
Published: April 2012

Vascular smooth muscle cells (VSMC) have been suggested to arise from various developmental sources during embryogenesis, depending on the vascular bed. However, evidence also points to a common subpopulation of vascular progenitor cells predisposed to VSMC fate in the embryo. In the present study, we use binary transgenic reporter mice to identify a Tie1
+
CD31
dim
vascular endothelial (VE)-cadherin
−
CD45
−
precursor that gives rise to VSMC in vivo in all vascular beds examined. This precursor does not represent a mature endothelial cell, because a VE-cadherin promoter-driven reporter shows no expression in VSMC during murine development. Blockade of Notch signaling in the Tie1
+
precursor cell, but not the VE-cadherin
+
endothelial cell, decreases VSMC investment of developing arteries, leading to localized hemorrhage in the embryo at the time of vascular maturation. However, Notch signaling is not required in the Tie1
+
precursor after establishment of a stable artery. Thus, Notch activity is required in the differentiation of a Tie1
+
local precursor to VSMC in a spatiotemporal fashion across all vascular beds.
Link between orientation and retinotopic maps in primary visual cortex
Authors: Paik Se-Bum , Ringach Dario L.
Published: April 2012

Maps representing the preference of neurons for the location and orientation of a stimulus on the visual field are a hallmark of primary visual cortex. It is not yet known how these maps develop and what function they play in visual processing. One hypothesis postulates that orientation maps are initially seeded by the spatial interference of ON- and OFF-center retinal receptive field mosaics. Here we show that such a mechanism predicts a link between the layout of orientation preferences around singularities of different signs and the cardinal axes of the retinotopic map. Moreover, we confirm the predicted relationship holds in tree shrew primary visual cortex. These findings provide additional support for the notion that spatially structured input from the retina may provide a blueprint for the early development of cortical maps and receptive fields. More broadly, it raises the possibility that spatially structured input from the periphery may shape the organization of primary sensory cortex of other modalities as well.
Midlife gene expressions identify modulators of aging through dietary interventions
Authors: Zhou Bing , Yang Liu , Li Shoufeng , Huang Jialiang , Chen Haiyang , Hou Lei , Wang Jinbo , Green Christopher D. , Yan Zhen , Huang Xun , Kaeberlein Matt , Zhu Li , Xiao Huasheng , Liu Yong , Han Jing-Dong J.
Published: April 2012

Dietary interventions are effective ways to extend or shorten lifespan. By examining midlife hepatic gene expressions in mice under different dietary conditions, which resulted in different lifespans and aging-related phenotypes, we were able to identify genes and pathways that modulate the aging process. We found that pathways transcriptionally correlated with diet-modulated lifespan and physiological changes were enriched for lifespan-modifying genes. Intriguingly, mitochondrial gene expression correlated with lifespan and anticorrelated with aging-related pathological changes, whereas peroxisomal gene expression showed an opposite trend. Both organelles produce reactive oxygen species, a proposed causative factor of aging. This finding implicates a contribution of peroxisome to aging. Consistent with this hypothesis, lowering the expression levels of peroxisome proliferation genes decreased the cellular peroxide levels and extended the lifespan of
Drosophila melanogaster
and
Caenorhabditis elegans
. These findings show that transcriptional changes resulting from dietary interventions can effectively reflect causal factors in aging and identify previously unknown or under-appreciated longevity pathways, such as the peroxisome pathway.
Kaposi’s sarcoma-associated herpesvirus interacts with EphrinA2 receptor to amplify signaling essential for productive infection
Authors: Chakraborty Sayan , Veettil Mohanan Valiya , Bottero Virginie , Chandran Bala
Published: April 2012

Kaposi’s sarcoma-associated herpesvirus (KSHV), etiologically associated with Kaposi’s sarcoma, uses integrins (α3β1, αVβ3, and αVβ5) and associated signaling to enter human dermal microvascular endothelial cells (HMVEC-d), an in vivo target of infection. KSHV infection activated c-Cbl, which induced the selective translocation of KSHV into lipid rafts (LRs) along with the α3β1, αVβ3, and xCT receptors, but not αVβ5. LR-translocated receptors were monoubiquitinated, leading to productive macropinocytic entry, whereas non-LR–associated αVβ5 was polyubiquitinated, leading to clathrin-mediated entry that was targeted to lysosomes. Because the molecule(s) that integrate signal pathways and productive KSHV macropinocytosis were unknown, we immunoprecipitated KSHV-infected LR fractions with anti-α3β1 antibodies and analyzed them by mass spectrometry. The tyrosine kinase EphrinA2 (EphA2), implicated in many cancers, was identified in this analysis. EphA2 was activated by KSHV. EphA2 was also associated with KSHV and integrins (α3β1 and αVβ3) in LRs early during infection. Preincubation of virus with soluble EphA2, knockdown of EphA2 by shRNAs, or pretreatment of cells with anti-EphA2 monoclonal antibodies or tyrosine kinase inhibitor dasatinib significantly reduced KSHV entry and gene expression. EphA2 associates with c-Cbl-myosin IIA and augmented KSHV-induced Src and PI3-K signals in LRs, leading to bleb formation and macropinocytosis of KSHV. EphA2 shRNA ablated macropinocytosis-associated signaling events, virus internalization, and productive nuclear trafficking of KSHV DNA. Taken together, these studies demonstrate that the EphA2 receptor acts as a master assembly regulator of KSHV-induced signal molecules and KSHV entry in endothelial cells and suggest that the EphA2 receptor is an attractive target for controlling KSHV infection.
BRD4 is an atypical kinase that phosphorylates Serine2 of the RNA Polymerase II carboxy-terminal domain
Authors: Devaiah Ballachanda N. , Lewis Brian A. , Cherman Natasha , Hewitt Michael C. , Albrecht Brian K. , Robey Pamela G. , Ozato Keiko , Sims Robert J. , Singer Dinah S.
Published: April 2012

The bromodomain protein, BRD4, has been identified recently as a therapeutic target in acute myeloid leukemia, multiple myeloma, Burkitt’s lymphoma, NUT midline carcinoma, colon cancer, and inflammatory disease; its loss is a prognostic signature for metastatic breast cancer. BRD4 also contributes to regulation of both cell cycle and transcription of oncogenes, HIV, and human papilloma virus (HPV). Despite its role in a broad range of biological processes, the precise molecular mechanism of BRD4 function remains unknown. We report that BRD4 is an atypical kinase that binds to the carboxyl-terminal domain (CTD) of RNA polymerase II and directly phosphorylates its serine 2 (Ser2) sites both in vitro and in vivo under conditions where other CTD kinases are inactive. Phosphorylation of the CTD Ser2 is inhibited in vivo by a BRD4 inhibitor that blocks its binding to chromatin. Our finding that BRD4 is an RNA polymerase II CTD Ser2 kinase implicates it as a regulator of eukaryotic transcription.
Refactoring the nitrogen fixation gene cluster fromKlebsiella oxytoca
Authors: Temme Karsten , Zhao Dehua , Voigt Christopher A.
Published: April 2012

Bacterial genes associated with a single trait are often grouped in a contiguous unit of the genome known as a gene cluster. It is difficult to genetically manipulate many gene clusters because of complex, redundant, and integrated host regulation. We have developed a systematic approach to completely specify the genetics of a gene cluster by rebuilding it from the bottom up using only synthetic, well-characterized parts. This process removes all native regulation, including that which is undiscovered. First, all noncoding DNA, regulatory proteins, and nonessential genes are removed. The codons of essential genes are changed to create a DNA sequence as divergent as possible from the wild-type (WT) gene. Recoded genes are computationally scanned to eliminate internal regulation. They are organized into operons and placed under the control of synthetic parts (promoters, ribosome binding sites, and terminators) that are functionally separated by spacer parts. Finally, a controller consisting of genetic sensors and circuits regulates the conditions and dynamics of gene expression. We applied this approach to an agriculturally relevant gene cluster fromKlebsiella oxytocaencoding the nitrogen fixation pathway for converting atmospheric N2to ammonia. The native gene cluster consists of 20 genes in seven operons and is encoded in 23.5 kb of DNA. We constructed a “refactored” gene cluster that shares little DNA sequence identity with WT and for which the function of every genetic part is defined. This work demonstrates the potential for synthetic biology tools to rewrite the genetics encoding complex biological functions to facilitate access, engineering, and transferability.
Nest-building orangutans demonstrate engineering know-how to produce safe, comfortable beds
Authors: van Casteren Adam , Sellers William I. , Thorpe Susannah K. S. , Coward Sam , Crompton Robin H. , Myatt Julia P. , Ennos A. Roland
Published: April 2012

Nest-building orangutans must daily build safe and comfortable nest structures in the forest canopy and do this quickly and effectively using the branches that surround them. This study aimed to investigate the mechanical design and architecture of orangutan nests and determine the degree of technical sophistication used in their construction. We measured the whole nest compliance and the thickness of the branches used and recorded the ways in which the branches were fractured. Branch samples were also collected from the nests and subjected to three-point bending tests to determine their mechanical properties. We demonstrated that the center of the nest is more compliant than the edges; this may add extra comfort and safety to the structure. During construction orangutans use the fact that branches only break half-way across in “greenstick” fracture to weave the main nest structure. They choose thicker branches with greater rigidity and strength to build the main structure in this way. They then detach thinner branches by following greenstick fracture with a twisting action to make the lining. These results suggest that orangutans exhibit a degree of technical knowledge and choice in the construction of nests.
Genetic, molecular, and biochemical basis of fungal tropolone biosynthesis
Authors: Davison Jack , al Fahad Ahmed , Cai Menghao , Song Zhongshu , Yehia Samar Y. , Lazarus Colin M. , Bailey Andrew M. , Simpson Thomas J. , Cox Russell J.
Published: April 2012

A gene cluster encoding the biosynthesis of the fungal tropolone stipitatic acid was discovered in
Talaromyces stipitatus
(
Penicillium stipitatum
) and investigated by targeted gene knockout. A minimum of three genes are required to form the tropolone nucleus: tropA encodes a nonreducing polyketide synthase which releases 3-methylorcinaldehyde; tropB encodes a FAD-dependent monooxygenase which dearomatizes 3-methylorcinaldehyde via hydroxylation at C-3; and tropC encodes a non-heme Fe(II)-dependent dioxygenase which catalyzes the oxidative ring expansion to the tropolone nucleus via hydroxylation of the 3-methyl group. The tropA gene was characterized by heterologous expression in
Aspergillus oryzae
, whereas tropB and tropC were successfully expressed in
Escherichia coli
and the purified TropB and TropC proteins converted 3-methylorcinaldehyde to a tropolone in vitro. Finally, knockout of the tropD gene, encoding a cytochrome P450 monooxygenase, indicated its place as the next gene in the pathway, probably responsible for hydroxylation of the 6-methyl group. Comparison of the
T. stipitatus
tropolone biosynthetic cluster with other known gene clusters allows clarification of important steps during the biosynthesis of other fungal compounds including the xenovulenes, citrinin, sepedonin, sclerotiorin, and asperfuranone.
Predator-induced macroevolutionary trends in Mesozoic crinoids
Authors: Gorzelak Przemysław , Salamon Mariusz A. , Baumiller Tomasz K.
Published: April 2012

Sea urchins are a major component of recent marine communities where they exert a key role as grazers and benthic predators. However, their impact on past marine organisms, such as crinoids, is hard to infer in the fossil record. Analysis of bite mark frequencies on crinoid columnals and comprehensive genus-level diversity data provide unique insights into the importance of sea urchin predation through geologic time. These data show that over the Mesozoic, predation intensity on crinoids, as measured by bite mark frequencies on columnals, changed in step with diversity of sea urchins. Moreover, Mesozoic diversity changes in the predatory sea urchins show a positive correlation with diversity of motile crinoids and a negative correlation with diversity of sessile crinoids, consistent with a crinoid motility representing an effective escape strategy. We contend that the Mesozoic diversity history of crinoids likely represents a macroevolutionary response to changes in sea urchin predation pressure and that it may have set the stage for the recent pattern of crinoid diversity in which motile forms greatly predominate and sessile forms are restricted to deep-water refugia.