bluuebunny/crossref_metadata_2025 huggingface dataset:
ROR1 can interact with TCL1 and enhance leukemogenesis in Eµ-TCL1 transgenic mice
Authors: Widhopf George F. , Cui Bing , Ghia Emanuela M. , Chen Liguang , Messer Karen , Shen Zhouxin , Briggs Steven P. , Croce Carlo M. , Kipps Thomas J.
Published: December 2013

Significance

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a type 1 protein expressed on chronic lymphocytic leukemia (CLL) B cells, but not on normal postpartum tissues. This study demonstrates that ROR1 can contribute to leukemogenesis and can bind to T-cell leukemia 1 (TCL1), a known coactivator of AKT. ROR1 can accelerate leukemogenesis when expressed together TCL1, leading to increased activation of AKT and enhanced leukemia-cell proliferation and resistance to apoptosis. Treatment of ROR1-expressing leukemia cells with an anti-ROR1 mAb could down-modulate ROR1, reduce phospho-AKT, and impair their capacity to engraft syngeneic mice. Collectively, our data demonstrate that ROR1 accelerates development/progression of leukemia and may be targeted for therapy of patients with CLL.
Rapid disorganization of mechanically interacting systems of mammary acini
Authors: Shi Quanming , Ghosh Rajarshi P. , Engelke Hanna , Rycroft Chris H. , Cassereau Luke , Sethian James A. , Weaver Valerie M. , Liphardt Jan T.
Published: December 2013

Significance

Tissue mechanics are important in differentiation and development but also in diseases like breast cancer. Most breast cancers start in mammary acini, which are basic anatomical units of the mammary gland. We found in a model system that mammary acini can coordinate their disorganization toward a malignant phenotype through long-range mechanical interactions. When two or more contractile acini are sufficiently close together, they can interact via collagen lines that form between them due to acinar contractility and the nonlinearity of collagen mechanics. Disorganization of interacting acini is more probable, rapid, and extensive than that of noninteracting acini. The results may help to better understand how extrinsic factors such as tissue architecture and mechanics contribute to tumor initiation and progression.
In vitro selection with artificial expanded genetic information systems
Authors: Sefah Kwame , Yang Zunyi , Bradley Kevin M. , Hoshika Shuichi , Jiménez Elizabeth , Zhang Liqin , Zhu Guizhi , Shanker Savita , Yu Fahong , Turek Diane , Tan Weihong , Benner Steven A.
Published: December 2013

Significance

Many chemicals are valuable because they bind to other molecules. Chemical theory cannot directly design “binders.” However, we might recreate in the laboratory the Darwinian processes that nature uses to create binders. This in vitro evolution uses nucleic acids as binders, libraries of DNA/RNA to survive a selection challenge before they can have “children” (systematic evolution of ligands by exponential enrichment, SELEX). Unfortunately, with only four nucleotides, natural DNA/RNA often yields only poor binders, perhaps because they are built from only four building blocks. Synthetic biology has increased the number of DNA/RNA building blocks, with tools to sequence, PCR amplify, and clone artificially expanded genetic information systems (AEGISs). We report here the first example of a SELEX using AEGIS, producing a molecule that binds to cancer cells.
Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage
Authors: Taira Naoe , Yamaguchi Tomoko , Kimura Junko , Lu Zheng-Guang , Fukuda Shinji , Higashiyama Shigeki , Ono Masaya , Yoshida Kiyotsugu
Published: December 2013

Significance

The tumor suppressive function of p53 is tightly regulated by its posttranslational modifications. Although Ser46 phosphorylation is a critical modification for apoptosis induction, a molecular mechanism by which Ser46-phosphorylated p53 induces apoptosis remains unclear. Here, we clarify that amphiregulin (AREG) is specifically induced in a Ser46 phosphorylation-specific manner. Notably, AREG colocalizes with DEAD-box RNA helicase p68 (DDX5) in the nucleus and regulates tumor suppressive microRNA biogenesis in response to DNA damage. These findings support a model in which Ser46-phosphorylated p53 orchestrates tumor suppressive microRNA expression in the apoptotic response to DNA damage.
Methanotrophy induces nitrogen fixation during peatland development
Authors: Larmola Tuula , Leppänen Sanna M. , Tuittila Eeva-Stiina , Aarva Maija , Merilä Päivi , Fritze Hannu , Tiirola Marja
Published: December 2013

Significance

In peatlands, the external sources of nitrogen are mainly atmospheric, but the atmospheric nitrogen deposition alone cannot explain the long-term annual nitrogen accumulation rates to these ecosystems. Because of methodological problems, methane-induced fixation of atmospheric dinitrogen gas has been previously overlooked as an additional nitrogen input mechanism. We found that the activity of methane-oxidizing bacteria provides not only carbon but also nitrogen to peat mosses and, thus, contributes to carbon and nitrogen accumulation in peatlands, which store approximately one-third of the global soil carbon pool. Our results imply that nitrogen fixation in wetlands may be strongly underestimated when methods inhibiting methane oxidizers are used.
Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus
Authors: Randall Crystal M. H. , Biswas Sunetra , Selen Catherine V. , Shisler Joanna L.
Published: December 2013

Significance

Viruses express proteins that circumvent immune responses. In some cases, these viral proteins are homologous to cellular proteins. For example the poxviral MC159 and MC160 proteins are homologous to cellular FLICE-like inhibitory protein (FLIP). Each protein inhibited IFN-β activation, identifying a unique function for FLIPs. Surprisingly, the viral proteins possessed different biological mechanisms for inhibition. MC159 bound to upstream activators of this pathway (namely TBK1 and IKKε) to inhibit IRF3 but MC160 did not. Moreover, the MC159 and MC160 regions responsible for inhibition did not overlap. Scientists can uncover new pathways of immune system regulation and new means for manipulating immune responses by comparing the molecular functions of these viral and cellular FLIPs.
Natural history-driven, plant-mediated RNAi-based study reveals
CYP6B46
’s role in a nicotine-mediated antipredator herbivore defense
Authors: Kumar Pavan , Pandit Sagar S. , Steppuhn Anke , Baldwin Ian T.
Published: December 2013

Significance

When hornworm (
Manduca sexta
) larvae feed on
Nicotiana attenuata
plants in native habitats, more disappear at night when they feed on transgenic, nicotine-free
N. attenuata
plants because wolf spiders (
Camptocosa parallela
) selectively prey on nicotine-free larvae. When larvae consume nicotine-replete plants, their midgut-expressed cytochrome P450 6B46 (
CYP6B46
) is upregulated. The larvae in which
CYP6B46
is silenced by plant-mediated RNAi excrete more of their ingested nicotine. Silencing
CYP6B46
impairs the mechanisms of passing ingested nicotine from the midgut to the hemolymph to be exhaled from the spiracles during spider attack. Spiders are deterred by this nicotine-rich halitosis. Thus, the
CYP6B46
-silenced larvae exhale less nicotine and become ready spider prey, demonstrating that
CYP6B46
functions to repurpose the normally excreted nicotine for defense.
Fenton chemistry at aqueous interfaces
Authors: Enami Shinichi , Sakamoto Yosuke , Colussi Agustín J.
Published: December 2013

Significance

The Fenton reaction, Fe
2+
+ H
2
O
2
, plays fundamental roles in vivo and in advanced oxidation processes. Its mechanism and the identity of the intermediates involved, however, remain controversial. Here we present direct, mass-specific evidence of the prompt formation of mono- and poly-iron Fe
IV
=O (ferryl) species on the surface of aqueous FeCl
2
microjets exposed to gaseous H
2
O
2
or O
3
beams. Remarkably, Fe
2+
ions at the aqueous surface react with H
2
O
2
and O
3
>10
3
times faster than Fe(H
2
O)
6
2+
in bulk water. Our results suggest that interfacial Fenton and Fenton-like chemistries could play a more significant role than hitherto envisioned.
Functional traits explain variation in plant life history strategies
Authors: Adler Peter B. , Salguero-Gómez Roberto , Compagnoni Aldo , Hsu Joanna S. , Ray-Mukherjee Jayanti , Mbeau-Ache Cyril , Franco Miguel
Published: December 2013

Significance

Plants have evolved diverse life history strategies to succeed in Earth’s varied environments. Some species grow quickly, produce copious seeds, and die within a few weeks. Other species grow slowly and rarely produce seeds but live thousands of years. We show that simple morphological measurements can predict where a species falls within the global range of life history strategies: species with large seeds, long-lived leaves, or dense wood have population growth rates influenced primarily by survival, whereas individual growth and fecundity have a stronger influence on the dynamics of species with small seeds, short-lived leaves, or soft wood. This finding increases the ability of scientists to represent complex population processes with a few easily measured character traits.
Role of ocean heat transport in climates of tidally locked exoplanets around M dwarf stars
Authors: Hu Yongyun , Yang Jun
Published: December 2013

Significance

Tidal-locking planets receive very uneven stellar heating because their one side permanently faces their stars and the other remains dark. While the dayside can be warm enough to sustain liquid water, the nightside could be so cold that any gases would condense out. Here, we perform simulations with a coupled atmosphere–ocean model to demonstrate the importance of exooceanography in determining the habitability of tidal-locking exoplanets around M dwarfs. We show that ocean heat transport can substantially extend the dayside habitable area and efficiently warm the nightside, so that atmosphere collapse does not occur. As greenhouse effect or stellar radiation is sufficiently strong, ocean heat transport can even cause global deglaciation. Ocean heat transport also likely narrows the width of M dwarfs’ habitable zone.
Resting-brain functional connectivity predicted by analytic measures of network communication
Authors: Goñi Joaquín , van den Heuvel Martijn P. , Avena-Koenigsberger Andrea , Velez de Mendizabal Nieves , Betzel Richard F. , Griffa Alessandra , Hagmann Patric , Corominas-Murtra Bernat , Thiran Jean-Philippe , Sporns Olaf
Published: December 2013

Significance

Patterns of distributed brain activity are thought to underlie virtually all aspects of cognition and behavior. In this paper, we explore the degree to which it is possible to predict such functional patterns from the network of anatomical connections that link brain regions. To this end, we use three separately acquired neuroimaging datasets recording anatomical and functional connections in the human brain. We apply several measures of network communication that are derived analytically from the brain’s anatomical network. Our principal finding is that such network measures can predict empirically measured functional connectivity at levels that exceed other modeling approaches. Our study sheds light on the important role of anatomical networks and communication processes in shaping the brain’s functional activity.
High-throughput platform for real-time monitoring of biological processes by multicolor single-molecule fluorescence
Authors: Chen Jin , Dalal Ravindra V. , Petrov Alexey N. , Tsai Albert , O’Leary Seán E. , Chapin Karen , Cheng Janice , Ewan Mark , Hsiung Pei-Lin , Lundquist Paul , Turner Stephen W. , Hsu David R. , Puglisi Joseph D.
Published: December 2013

Significance

Zero-mode waveguides (ZMWs) provide a powerful technology for studying single-molecule real-time dynamics of biological systems. However, difficulties in instrumental implementation and ZMW fabrication prevented their widespread use. Here, we modify a commercially available ZMW-based DNA sequencer for use as a multipurpose single-molecule fluorescence instrument. The instrumentation presented here allows access to ZMWs for the general biophysics community for high-throughput multiplexed dynamics of single biological molecules.
Poleward expansion of mangroves is a threshold response to decreased frequency of extreme cold events
Authors: Cavanaugh Kyle C. , Kellner James R. , Forde Alexander J. , Gruner Daniel S. , Parker John D. , Rodriguez Wilfrid , Feller Ilka C.
Published: December 2013

Significance

Coastal mangrove forests support a diverse array of associated species and provide ecosystem services to human communities. Mangroves cannot tolerate extreme freezing temperatures and so are generally limited to tropical environments. However, climate change in the form of increasing temperatures has the potential to facilitate increases in mangrove abundance near tropical–temperate transition zones. Here, we use 28 y of satellite imagery to demonstrate that increases in mangrove area have already occurred along the northeast coast of Florida. These increases correspond to decreases in the frequency of extreme cold events in this region. We also identify a temperature-related ecological threshold of −4°C. These results suggest that landscape-scale increases in mangrove area may occur in other regions where this threshold is crossed.
Evolutionary genetics and implications of small size and twinning in callitrichine primates
Authors: Harris R. Alan , Tardif Suzette D. , Vinar Tomas , Wildman Derek E. , Rutherford Julienne N. , Rogers Jeffrey , Worley Kim C. , Aagaard Kjersti M.
Published: December 2013

Significance

New World monkeys (NWMs) are characterized by an extensive size range, and clawed NWMs (callitrichines) such as marmosets manifest diminutive size and unique reproductive adaptations such as twinning. Evolutionary explanations have been proposed for these traits, and with the common marmoset genome assembly the genetic underpinnings of these traits can now be explored. Callitrichine-specific nonsynonymous substitutions were identified inGDF9,BMP15, BMP4, andWFIKKN1. We postulate that positive selection affected NWM growth patterns, with callitrichine miniaturization coevolving with a series of reproductive adaptations that bear benefit when gestating multiples. Given the high rate of morbidity and mortality with human twins, future studies into callitrichine genomic adaptations will undoubtedly lead to unique insights of benefit to their human counterparts.
Role of intermediate phase for stable cycling of Na
7
V
4
(P
2
O
7
)
4
PO
4
in sodium ion battery
Authors: Lim Soo Yeon , Kim Heejin , Chung Jaehoon , Lee Ji Hoon , Kim Byung Gon , Choi Jeon-Jin , Chung Kyung Yoon , Cho Woosuk , Kim Seung-Joo , Goddard William A. , Jung Yousung , Choi Jang Wook
Published: December 2013

Significance

Utilizing low-cost materials, sodium ion batteries (SIBs) are beginning to attract considerable attention, particularly for large-scale utility grid applications. However, electrochemical performance of most SIB active materials is still insufficient for various practical applications. In the current study, we discovered a vanadium-based ortho-diphosphate, Na
7
V
4
(P
2
O
7
)
4
PO
4
, or VODP, that holds exceptional electrochemical properties represented by well-defined high voltage profiles at 3.88 V (vs. Na/Na
+
) and substantial capacity retention over 1,000 cycles. A theoretical analysis suggests that an intermediate phase encountered during phase transformation of VODP is crucial for better kinetics during battery operations, which can be expanded as a general principle in understanding diverse battery materials.
TRIM14 is a mitochondrial adaptor that facilitates retinoic acid-inducible gene-I–like receptor-mediated innate immune response
Authors: Zhou Zhuo , Jia Xue , Xue Qinghua , Dou Zhixun , Ma Yijie , Zhao Zhendong , Jiang Zhengfan , He Bin , Jin Qi , Wang Jianwei
Published: December 2013

Significance

The innate immune system plays a key role in host defense that involves the detection of microbial components and a series of signaling events that lead to production of interferons and cytokines. Recently, the identification of mitochondrial antiviral-signaling (MAVS) protein placed mitochondria at the forefront of the innate immune response against virus infection. However, how the MAVS signaling complex is assembled and regulated on the mitochondria outer membrane is only partially understood. Here we show that tripartite motif 14 (TRIM14) facilitates the assembly of the MAVS complex assembly. Upon virus infection, TRIM14 recruits NF-κB essential modulator (NEMO) to the MAVS complex via ubiquitin chains. Knockdown of TRIM14 disrupts the MAVS–NEMO association and attenuates the antiviral response. Our results thus provide a missing link in MAVS-mediated innate immune signaling.
Structural mechanisms of PriA-mediated DNA replication restart
Authors: Bhattacharyya Basudeb , George Nicholas P. , Thurmes Tiffany M. , Zhou Ruobo , Jani Niketa , Wessel Sarah R. , Sandler Steven J. , Ha Taekjip , Keck James L.
Published: December 2013

Significance

This study describes the crystal structures of the full-length PriA DNA helicase, a multifunctional enzyme that mediates the essential process of restarting prematurely terminated DNA replication reactions in bacteria. Our findings reveal how PriA is able to recognize replication restart substrates through structure-specific DNA binding and interactions with the ssDNA-binding protein and how it exposes ssDNA that could be used to reload the replisome and reinitiate replication. These observations shed light on the physical mechanisms that allow cells to survive the common and potentially lethal problems posed by incomplete genome replication.
Hydrophobic plug functions as a gate in voltage-gated proton channels
Authors: Chamberlin Adam , Qiu Feng , Rebolledo Santiago , Wang Yibo , Noskov Sergei Y. , Larsson H. Peter
Published: December 2013

Significance

Voltage-gated proton (Hv1) channels play important roles in various physiological processes, such as the innate immune response. However, the mechanism by which this channel closes and opens its proton permeation pathways is unknown, due to the lack of structural information about the closed and open states of the channel. This study uses both simulation and experimental approaches to develop models of the closed and open states of the Hv1 channel. These models suggest a mechanism for how the channel closes and opens. The models also suggest a mechanism explaining why a blocker only binds to the open state of the channel. These structural models will be essential for future investigations of this channel and the development of new pharmacological blockers.
Differential processing of
Arabidopsis
ubiquitin-like Atg8 autophagy proteins by Atg4 cysteine proteases
Authors: Woo Jongchan , Park Eunsook , Dinesh-Kumar S. P.
Published: December 2013

Significance

Autophagy is a highly regulated biological process for recycling or degrading cellular contents in response to environmental stimuli. Atg4 cysteine protease-mediated processing of Atg8 proteins is required for formation of intracellular vesicles, autophagosomes, which carry cellular cargoes to the vacuole/lysosome. Because the
Arabidopsis
plant contains nine AtAtg8 and two AtAtg4 proteins, we have developed unique AtAtg8 synthetic substrates to determine AtAtg4s cleavage specificity. We show that AtAtg4a is more active and cleaves all AtAtg8s efficiently compared with AtAtg4b. The AtAtg8 synthetic substrate can be efficiently incorporated to autophagosomes in plant cells and this requires endogenous AtAtg4s. The AtAtg8 synthetic substrates described here are suitable to screen for in vitro and in vivo autophagy regulators.
Calmodulin regulates dimerization, motility, and lipid binding of
Leishmania
myosin XXI
Authors: Batters Christopher , Ellrich Heike , Helbig Constanze , Woodall Katy Anna , Hundschell Christian , Brack Dario , Veigel Claudia
Published: December 2013

Significance

Myosin XXI is the only myosin isoform expressed in the
Leishmania
parasite. The myosin-XXI homozygous knockout is lethal, and a reduction in expression levels leads to loss of endocytosis and affects other intracellular trafficking processes. In this paper we show that myosin XXI can adopt a monomeric or dimeric state. The states are determined by calmodulin binding to an IQ motif that, when bound, prevents dimerization of a coiled-coil motif. In the monomeric state the motor binds phospholipids and is motile whereas the dimeric state is unable to bind lipids or to generate motility, but can cross-link actin filaments. Regulation of dimerization, motility, and lipid binding by calmodulin is a mechanism for the myosin family of motor proteins.
The inner rod protein controls substrate switching and needle length in a
Salmonella
type III secretion system
Authors: Lefebre Matthew D. , Galán Jorge E.
Published: December 2013

Significance

Type III secretion systems are multiprotein nanomachines with the capacity to inject bacterial proteins into eukaryotic cells that are used by bacterial symbionts or pathogens to interact with their hosts. The main component of these machines is the needle complex, a multiprotein organelle composed of a bacterial envelope-associated multiring base and a filament-like structure, the needle, that projects from the bacterial surface and is linked to the base by an inner rod. Here we have studied the inner rod in detail and provided important insight into the mechanism of assembly and function of type III secretion machines. Understanding the function of type III secretion machines could lead to the development of novel antimicrobials.
IRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation
Authors: Lin Keng-Mean , Hu Wei , Troutman Ty Dale , Jennings Michelle , Brewer Travis , Li Xiaoxia , Nanda Sambit , Cohen Philip , Thomas James A. , Pasare Chandrashekhar
Published: December 2013

Significance

Toll-like receptors recognize conserved molecules that are expressed by both harmless (commensal) and harmful (virulent) microbes. Another set of receptors, nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed in the cytosol and recognize virulence factors and toxins from pathogenic microbes. Previous studies on TLRs and NLRs have suggested that TLR signaling primes the NLR inflammasome pathway. Here we discovered that TLRs, via the signaling molecule IL-1 receptor-associated kinase, directly regulate activation of a specific NLR, nucleotide binding and oligomerization, leucine-rich repeat, pyrin domain-containing 3 (NLRP3). This is important because when infection occurs, the virulent/pathogenic microorganisms activate both of these receptors. We also found that simultaneous activation of TLRs and NLRP3 is important for rapid innate immune response by the host.
Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders
Authors: Dukart Juergen , Regen Francesca , Kherif Ferath , Colla Michael , Bajbouj Malek , Heuser Isabella , Frackowiak Richard S. , Draganski Bogdan
Published: December 2013

Significance

Electroconvulsive therapy is controversial: How does a major electrical discharge over half the brain result in recovery in disorders such as refractory major depression and manic depression, which are apparently different diseases? We find local but not general brain anatomy changes following electroconvulsive therapy that are differently distributed in each disease, and the areas affected are those implicated as abnormal in each disorder. An interaction between electroconvulsive therapy and specific pathology appears to be responsible for the therapeutic effect. Our results have implications for other electrically based brain treatments, such as deep brain stimulation and transcranial magnetic stimulation.
Self-assembled lipid and membrane protein polyhedral nanoparticles
Authors: Basta Tamara , Wu Hsin-Jui , Morphew Mary K. , Lee Jonas , Ghosh Nilanjan , Lai Jeffrey , Heumann John M. , Wang Keeshia , Lee Y. C. , Rees Douglas C. , Stowell Michael H. B.
Published: December 2013

Significance

An alternate strategy to tubular or 2D crystals for high-resolution membrane protein structure determination by electron microscopy has been developed. Homogeneous polyhedral proteoliposomes of defined symmetry were prepared from theEscherichia colimechanosensitive channel of small conductance (MscS). These membrane protein polyhedral nanoparticles (MPPNs) were analyzed by electron cryomicroscopy that established that they contain 24 MscS heptamers related by octahedral symmetry wherein the individual MscS conformation resembles the nonconducting state. We further demonstrate the development of a membraneless microfluidic device that can facilitate the preparation of a variety of MPPNs, with future applications including structural studies of membrane proteins in the presence of transmembrane gradients, as well as drug delivery carriers or as templates for inorganic nanoparticle formation.
Positive regulatory role of strigolactone in plant responses to drought and salt stress
Authors: Ha Chien Van , Leyva-González Marco Antonio , Osakabe Yuriko , Tran Uyen Thi , Nishiyama Rie , Watanabe Yasuko , Tanaka Maho , Seki Motoaki , Yamaguchi Shinjiro , Dong Nguyen Van , Yamaguchi-Shinozaki Kazuko , Shinozaki Kazuo , Herrera-Estrella Luis , Tran Lam-Son Phan
Published: December 2013

Significance

Environmental stresses, such as drought and high salinity, adversely affect plant growth and productivity. Although various phytohormones are known to be involved in regulation of plant stress responses, the role of strigolactone (SL) in this important process remains elusive. By using different molecular and physiological approaches, we provide compelling evidence that, in
Arabidopsis
, SL acts as positive regulator of plant responses to drought and salt stress, which was associated with shoot- rather than root-related traits. Comparative transcriptome analysis suggests that plants integrate multiple hormone-response pathways—at least SL, abscisic acid, and cytokinin pathways—for adaptation to environmental stress. Our findings demonstrate that genetic modulation of SL content/response could provide a new approach for development of crops with improved stress tolerance.
Apo-bacteriophytochromes modulate bacterial photosynthesis in response to low light
Authors: Fixen Kathryn R. , Baker Anna W. , Stojković Emina A. , Beatty J. Thomas , Harwood Caroline S.
Published: December 2013

Significance

Bacteriophytochromes (BphPs) are regulatory proteins that bind a light-absorbing chromophore called biliverdin. Recombinant BphPs show promise for use in regulating neuron function in mammals with light. We explored the possibility that BphPs may sense cues in addition to light. Our motivation was that biliverdin requires oxygen for its synthesis, and some bacteria use BphPs to control photosynthesis in the absence of oxygen. We found that the photosynthetic bacterium
Rhodopseudomonas palustris
requires two BphP proteins to sense low light when grown in the absence of oxygen; however, the BphPs do not need to have their chromophore to sense low light intensities. BphPs may respond to intracellular signals, such as reducing conditions, in addition to light to regulate downstream functions.
Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists
Authors: Jaszberenyi Miklos , Rick Ferenc G. , Popovics Petra , Block Norman L. , Zarandi Marta , Cai Ren-Zhi , Vidaurre Irving , Szalontay Luca , Jayakumar Arumugam R. , Schally Andrew V.
Published: December 2013

Significance

Growth hormone-releasing hormone (GHRH) and its agonistic analogs, besides augmenting the release of growth hormone from the pituitary, can exert direct stimulatory effects on various extrapituitary tissues. Present oncologic evaluation of growth of a glioblastoma cell line revealed that the combination of GHRH agonist, JI-34, with doxorubicin (DOX) produced greater inhibition in vivo than either drug alone. In vitro, JI-34 also potentiated the effects of DOX, decreased the expression of the neuroectodermal stem-cell antigen, nestin, and up-regulated the glial maturation marker, GFAP. These findings indicate that GHRH agonists can induce differentiation of cancer cells, increasing the response to DOX. These observations expand the known spectrum of activities of GHRH and its analogs and have potential clinical implications for therapy.
TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability
Authors: Germann Susanne M. , Schramke Vera , Pedersen Rune Troelsgaard , Gallina Irene , Eckert-Boulet Nadine , Oestergaard Vibe H. , Lisby Michael
Published: December 2013

DNA anaphase bridges are a potential source of genome instability that may lead to chromosome breakage or nondisjunction during mitosis. Two classes of anaphase bridges can be distinguished: DAPI-positive chromatin bridges and DAPI-negative ultrafine DNA bridges (UFBs). Here, we establish budding yeast Saccharomyces cerevisiae and the avian DT40 cell line as model systems for studying DNA anaphase bridges and show that TopBP1/Dpb11 plays an evolutionarily conserved role in their metabolism. Together with the single-stranded DNA binding protein RPA, TopBP1/Dpb11 binds to UFBs, and depletion of TopBP1/Dpb11 led to an accumulation of chromatin bridges. Importantly, the NoCut checkpoint that delays progression from anaphase to abscission in yeast was activated by both UFBs and chromatin bridges independently of Dpb11, and disruption of the NoCut checkpoint in Dpb11-depleted cells led to genome instability. In conclusion, we propose that TopBP1/Dpb11 prevents accumulation of anaphase bridges via stimulation of the Mec1/ATR kinase and suppression of homologous recombination.
Sending sisters their separate ways
Authors: Leslie Mitch
Published: December 2013

Repair protein helps resolve entanglements between sister chromatids.
The “mapping out” approach: effectiveness of marine spatial management options in European coastal waters
Authors: Soma Katrine , Ramos Jorge , Bergh Øivind , Schulze Torsten , van Oostenbrugge Hans , van Duijn Arie Pieter , Kopke Kathrin , Stelzenmüller Vanessa , Grati Fabio , Mäkinen Timo , Stenberg Claus , Buisman Erik
Published: December 2013

Marine spatial management is challenged by complex situations in European countries where multiple stakeholder interests and many management options have to be balanced. EU policy initiatives such as the proposed Marine Spatial Planning Directive, are in different ways targeting area allocation in European waters. In this circumstance, EU marine management needs assessments based on a satisfactory evaluation framework design that can ensure a transparent treatment of different types of information including interests, values, and facts. The main goal of this article is to introduce an evaluation framework applicable to marine management in European countries. This so-called CoExist framework maps out different types of relevant knowledge to assess future possibilities for use or no-use of marine areas and links this with appropriate management measures. The CoExist framework is based on the principles of ensuring transparent treatment of different types of information as well as appropriate stakeholder representation which can ensure legitimacy. Empirical findings in six European case studies have been obtained while conducting the CoExist framework. Applying the basic principles of the CoExist framework when planning future management directions of the coexistence of multiple activities in the long-run will expectedly affect the ecological and social-cultural goals by counterbalancing the economic ones.
Poor taxonomical knowledge of larval fish prey preference is impeding our ability to assess the existence of a “critical period” driving year-class strength
Authors: Robert Dominique , Murphy Hannah M. , Jenkins Gregory P. , Fortier Louis
Published: December 2013

Despite 100 years of research testing the link between prey availability during the larval stage and year-class strength, field-based evidence for Hjort's “critical period” hypothesis remains equivocal. Here, we argue that a minority of past studies have relied on sufficient taxonomical knowledge of larval fish prey preference to reveal the potential effects of variability in zooplankton prey production on larval vital rates and year-class strength. In contrast to the juvenile and adult stages, larval fish diet and prey field are often poorly resolved, resulting in the inclusion of zooplankton taxa that do not actually contribute to the diet as part of the prey field considered by fisheries scientists. Recent studies have demonstrated that when accounting for prey selectivity, the expected positive relationships between preferred prey availability and larval feeding success, growth and survival are revealed. We strongly recommend that laboratories conducting research on larval fish trophodynamics take prey selectivity into account and acquire the necessary taxonomic expertise for providing valid assessments of the influence of prey availability on larval vital rates. We make the prediction that the proportion of studies supporting the existence of a “critical period” will increase proportionally to the progress of knowledge on prey preference during the early larval stage.
BOFFFFs: on the importance of conserving old-growth age structure in fishery populations
Authors: Hixon Mark A. , Johnson Darren W. , Sogard Susan M.
Published: December 2013

The value of big old fat fecund female fish (BOFFFFs) in fostering stock productivity and stability has long been underappreciated by conventional fisheries science and management, although Hjort (1914) indirectly alluded to the importance of maternal effects. Compared with smaller mature females, BOFFFFs in a broad variety of marine and freshwater teleosts produce far more and often larger eggs that may develop into larvae that grow faster and withstand starvation better. As (if not more) importantly, BOFFFFs in batch-spawning species tend to have earlier and longer spawning seasons and may spawn in different locations than smaller females. Such features indicate that BOFFFFs are major agents of bet-hedging strategies that help to ensure individual reproductive success in environments that vary tremendously in time and space. Even if all else were equal, BOFFFFs can outlive periods that are unfavourable for successful reproduction and be ready to spawn profusely and enhance recruitment when favourable conditions return (the storage effect). Fishing differentially removes BOFFFFs, typically resulting in severe truncation of the size and age structure of the population. In the worst cases, fishing mortality acts as a powerful selective agent that inhibits reversal of size and age truncation, even if fishing intensity is later reduced. Age truncation is now known to destabilize fished populations, increasing their susceptibility to collapse. Although some fisheries models are beginning to incorporate maternal and other old-growth effects, most continue to treat all spawning-stock biomass as identical: many small young females are assumed to contribute the same to stock productivity as an equivalent mass of BOFFFFs. A growing body of knowledge dictates that fisheries productivity and stability would be enhanced if management conserved old-growth age structure in fished stocks, be it by limiting exploitation rates, by implementing slot limits, or by establishing marine reserves, which are now known to seed surrounding fished areas via larval dispersal. Networks of marine reserves are likely to be the most effective means of ensuring that pockets of old-growth age structure survive throughout the geographic range of demersal species.
Quantum anomalous Hall effect
Authors: He Ke , Wang Yayu , Xue Qi-Kun
Published: December 2013

Hall effect is a well-known electromagnetic phenomenon that has been widely applied in the semiconductor industry. The quantum Hall effect discovered in two-dimensional electronic systems under a strong magnetic field provided new insights into condensed matter physics, especially the topological aspect of electronic states. The quantum anomalous Hall effect is a special kind of the quantum Hall effect that occurs without a magnetic field. It has long been sought after because its realization will significantly facilitate the studies and applications of the quantum Hall physics. In this paper, we review how the idea of the quantum anomalous Hall effect was developed and how the effect was finally experimentally realized in thin films of a magnetically doped topological insulator.
Polynomials for crystal frameworks and the rigid unit mode spectrum
Authors: Power S. C.
Published: December 2013

To each discrete translationally periodic bar-joint framework

in

, we associate a matrix-valued function

defined on the
d
-torus. The rigid unit mode (RUM) spectrum

of

is defined in terms of the multi-phases of phase-periodic infinitesimal flexes and is shown to correspond to the singular points of the function

and also to the set of wavevectors of harmonic excitations which have vanishing energy in the long wavelength limit. To a crystal framework in Maxwell counting equilibrium, which corresponds to

being square, the determinant of

gives rise to a unique multi-variable polynomial

. For ideal zeolites, the algebraic variety of zeros of

on the
d
-torus coincides with the RUM spectrum. The matrix function is related to other aspects of idealized framework rigidity and flexibility, and in particular leads to an explicit formula for the number of supercell-periodic floppy modes. In the case of certain zeolite frameworks in dimensions two and three, direct proofs are given to show the maximal floppy mode property (order
N
). In particular, this is the case for the cubic symmetry sodalite framework and some other idealized zeolites.
Fragmentary and incidental behaviour of columns, slabs and crystals
Authors: Whiteley Walter
Published: December 2013

Between the study of small finite frameworks and infinite incidentally periodic frameworks, we find the real materials which are large, but finite, fragments that fit into the infinite periodic frameworks. To understand these materials, we seek insights from both (i) their analysis as large frameworks with associated geometric and combinatorial properties (including the geometric repetitions) and (ii) embedding them into appropriate infinite periodic structures with motions that may break the periodic structure. A review of real materials identifies a number of examples with a local appearance of ‘unit cells’ which repeat under isometries but perhaps in unusual forms. These examples also refocus attention on several new classes of infinite ‘periodic’ frameworks: (i) columns—three-dimensional structures generated with one repeating isometry and (ii) slabs—three-dimensional structures with two independent repeating translations. With this larger vision of structures to be studied, we find some patterns and partial results that suggest new conjectures as well as many additional open questions. These invite a search for new examples and additional theorems.
Flexibility mechanisms in ideal zeolite frameworks
Authors: Treacy M. M. J. , Dawson C. J. , Kapko V. , Rivin I.
Published: December 2013

Zeolites are microporous crystalline aluminosilicate materials whose atomic structures can be usefully modelled in purely mechanical terms as stress-free periodic trusses constructed from rigid corner-connected SiO
4
and AlO
4
tetrahedra. When modelled this way,
all
of the known synthesized zeolite frameworks exhibit a range of densities, known as the flexibility window, over which they satisfy the framework mechanical constraints. Within the flexibility window internal stresses are accommodated by force-free coordinated rotations of the tetrahedra about their apices (oxygen atoms). We use rigidity theory to explore the folding mechanisms within the flexibility window, and derive an expression for the configurational entropic density throughout the flexibility window. By comparison with the structures of pure silica zeolite materials, we conclude that configurational entropy associated with the flexibility modes is not a dominant thermodynamic term in most bulk zeolite crystals. Nevertheless, the presence of a flexibility window in an idealized hypothetical tetrahedral framework may be thermodynamically important at the nucleation stage of zeolite formation, suggesting that flexibility is a strong indicator that the topology is realizable as a zeolite. Only a small fraction of the vast number of hypothetical zeolites that are known exhibit flexibility. The absence of a flexibility window may explain why so few hypothetical frameworks are realized in nature.
Group-theoretic insights on the vibration of symmetric structures in engineering
Authors: Zingoni Alphose
Published: December 2013

Group theory has been used to study various problems in physics and chemistry for many years. Relatively recently, applications have emerged in engineering, where problems of the vibration, bifurcation and stability of systems exhibiting symmetry have been studied. From an engineering perspective, the main attraction of group-theoretic methods has been their potential to reduce computational effort in the analysis of large-scale problems. In this paper, we focus on vibration problems in structural mechanics and reveal some of the insights and qualitative benefits that group theory affords. These include an appreciation of all the possible symmetries of modes of vibration, the prediction of the number of modes of a given symmetry type, the identification of modes associated with the same frequencies, the prediction of nodal lines and stationary points of a vibrating system, and the untangling of clustered frequencies.
Two exactly soluble models of rigidity percolation
Authors: Thorpe M. F. , Stinchcombe R. B.
Published: December 2013

We summarize results for two exactly soluble classes of bond-diluted models for rigidity percolation, which can serve as a benchmark for numerical and approximate methods. For bond dilution problems involving rigidity, the number of floppy modes
F
plays the role of a free energy. Both models involve pathological lattices with two-dimensional vector displacements. The
first model
involves hierarchical lattices where renormalization group calculations can be used to give exact solutions. Algebraic scaling transformations produce a transition of the second order, with an unstable critical point and associated scaling laws at a mean coordination 〈
r
〉=4.41, which is above the ‘mean field’ value 〈
r
〉=4 predicted by Maxwell constraint counting. The order parameter exponent associated with the spanning rigid cluster geometry is
β
=0.0775 and that associated with the divergence of the correlation length and the anomalous lattice dimension
d
is
dν
=3.533. The
second model
involves Bethe lattices where the rigidity transition is massively first order by a mean coordination 〈
r
〉=3.94 slightly below that predicted by Maxwell constraint counting. We show how a Maxwell equal area construction can be used to locate the first-order transition and how this result agrees with simulation results on larger random-bond lattices using the pebble game algorithm.
Periodic planar disc packings
Authors: Connelly Robert , Dickinson William
Published: December 2013

Several conditions are given when a packing of equal discs in a torus is locally maximally dense, where the torus is defined as the quotient of the plane by a two-dimensional lattice. Conjectures are presented that claim that the density of any collectively jammed packing, whose graph does not consist of all triangles, and the torus lattice is the standard triangular lattice, is at most

, where
n
is the number of packing discs in the torus. Several classes of collectively jammed packings are presented where the conjecture holds.
On the flexibility and symmetry of overconstrained mechanisms
Authors: Stachel Hellmuth
Published: December 2013

In kinematics, a framework is called overconstrained if its continuous flexibility is caused by particular dimensions; in the generic case, a framework of this type is rigid. Famous examples of overconstrained structures are the Bricard octahedra, the Bennett isogram, the Grünbaum framework, Bottema's 16-bar mechanism, Chasles’ body–bar framework, Burmester's focal mechanism or flexible quad meshes. The aim of this paper is to present some examples in detail and to focus on their symmetry properties. It turns out that only for a few is a global symmetry a necessary condition for flexibility. Sometimes, there is a hidden symmetry, and in some cases, for example, at the flexible type-3 octahedra or at discrete Voss surfaces, there is only a local symmetry. However, there remain overconstrained frameworks where the underlying algebraic conditions for flexibility have no relation to symmetry at all.
How does symmetry impact the flexibility of proteins?
Authors: Schulze Bernd , Sljoka Adnan , Whiteley Walter
Published: December 2013

It is well known that (i) the flexibility and rigidity of proteins are central to their function, (ii) a number of oligomers with several copies of individual protein chains assemble with symmetry in the native state and (iii) added symmetry sometimes leads to added flexibility in structures. We observe that the most common symmetry classes of protein oligomers are also the symmetry classes that lead to increased flexibility in certain three-dimensional structures—and investigate the possible significance of this coincidence. This builds on the well-developed theory of generic rigidity of body–bar frameworks, which permits an analysis of the rigidity and flexibility of molecular structures such as proteins via fast combinatorial algorithms. In particular, we outline some very simple counting rules and possible algorithmic extensions that allow us to predict continuous symmetry-preserving motions in body–bar frameworks that possess non-trivial point-group symmetry. For simplicity, we focus on dimers, which typically assemble with twofold rotational axes, and often have allosteric function that requires motions to link distant sites on the two protein chains.
The rigidity of periodic body–bar frameworks on the three-dimensional fixed torus
Authors: Ross Elissa
Published: December 2013

We present necessary and sufficient conditions for the generic rigidity of body–bar frameworks on the three-dimensional fixed torus. These frameworks correspond to infinite periodic body–bar frame-works in

with a fixed periodic lattice.
Frameworks with crystallographic symmetry
Authors: Borcea Ciprian S. , Streinu Ileana
Published: December 2013

Periodic frameworks with crystallographic symmetry are investigated from the perspective of a general deformation theory of periodic bar-and-joint structures in Euclidean spaces of arbitrary dimension. It is shown that natural parametrizations provide affine section descriptions for families of frameworks with a specified graph and symmetry. A simple geometrical setting for displacive phase transitions is obtained. Upper bounds are derived for the number of realizations of minimally rigid periodic graphs.