bluuebunny/crossref_metadata_2025 huggingface dataset:
Human infrared vision is triggered by two-photon chromophore isomerization
Authors: Palczewska Grazyna , Vinberg Frans , Stremplewski Patrycjusz , Bircher Martin P. , Salom David , Komar Katarzyna , Zhang Jianye , Cascella Michele , Wojtkowski Maciej , Kefalov Vladimir J. , Palczewski Krzysztof
Published: December 2014

Significance

This study resolves a long-standing question about the ability of humans to perceive near infrared radiation (IR) and identifies a mechanism driving human IR vision. A few previous reports and our expanded psychophysical studies here reveal that humans can detect IR at wavelengths longer than 1,000 nm and perceive it as visible light, a finding that has not received a satisfactory physical explanation. We show that IR light activates photoreceptors through a nonlinear optical process. IR light also caused photoisomerization of purified pigments and a model chromophore compound. These observations are consistent with our quantum mechanical model for the energetics of two-photon activation of rhodopsin. Thus, humans can perceive IR light via two-photon isomerization of visual pigment chromophores.
Multiple functional therapeutic effects of the estrogen receptor β agonist indazole-Cl in a mouse model of multiple sclerosis
Authors: Moore Spencer M. , Khalaj Anna J. , Kumar Shalini , Winchester Zachary , Yoon JaeHee , Yoo Timothy , Martinez-Torres Leonardo , Yasui Norio , Katzenellenbogen John A. , Tiwari-Woodruff Seema Kaushalya
Published: December 2014

Significance

In the search for effective multiple sclerosis treatment, much effort has been invested in estrogens and estrogen receptor (ER) agonists because of their neuroprotective benefits. However, because estrogens can produce ERα-based feminizing effects and cancer, ERβ agonists represent more desirable therapeutic candidates. The structurally unique ERβ ligand indazole chloride (Ind-Cl), a halogen-substituted phenyl-2H-indazole core, is a preclinical development candidate with a strong dossier. Our results indicate that Ind-Cl is effective in functionally ameliorating disease even when treatment is initiated at peak experimental autoimmune encephalomyelitis clinical disease. Ind-Cl’s immunomodulatory and direct remyelinating effects result in motor dysfunction amelioration. These findings support Ind-Cl's potential to provide unique therapeutic benefits to patients with multiple sclerosis, as well as patients affected by other demyelinating disorders.
Evolutionary limits to cooperation in microbial communities
Authors: Oliveira Nuno M. , Niehus Rene , Foster Kevin R.
Published: December 2014

Significance

Microbes form dense and diverse communities that affect every aspect of our lives. Microbial communities are often viewed as cooperative networks with species working together toward a common goal. Here, we critically evaluate this view using an ecoevolutionary model. We show that cooperating with other species can be a poor evolutionary strategy, because it renders a cell dependent on species that may not be nearby. Moreover, when cooperative exchanges do evolve, they are inefficient and reduce the productivity of the community. Evolution by natural selection then limits the potential for productive cooperation between microbial species. We argue that understanding these limits and how to overcome them will be key to engineering microbial communities for our own ends.
Vibrio
effector protein VopQ inhibits fusion of V-ATPase–containing membranes
Authors: Sreelatha Anju , Bennett Terry L. , Carpinone Emily M. , O’Brien Kevin M. , Jordan Kamyron D. , Burdette Dara L. , Orth Kim , Starai Vincent J.
Published: December 2014

Significance

Fusion of intracellular membranes is involved in many critical cellular processes, such as neurotransmission, protein trafficking, and in the lysosomal degradation of invading bacterial pathogens. Accordingly, some intracellular bacterial pathogens use protein effectors to alter host membrane fusion directly as a survival mechanism. In this study, we show that the
Vibrio
secreted effector, VopQ, is a potent inhibitor of yeast homotypic vacuole fusion in vitro. Although VopQ was shown to deacidify yeast vacuoles via its known V-type H
+
-ATPase (V-ATPase)-binding and channel-forming activities, its ability to inhibit vacuole fusion does not depend on channel-forming activity. Our studies suggest that yeast vacuole fusion is not regulated by lumenal acidification and identify a reagent to study the V-ATPase role in some membrane fusion events.
Power transduction of actin filaments ratcheting in vitro against a load
Authors: Démoulin Damien , Carlier Marie-France , Bibette Jérôme , Baudry Jean
Published: December 2014

Significance

How the continuous polymerization of actin filaments pushes the cell membrane forward in migrating cells is an intriguing issue that has yet to be fully understood. Molecular mechanisms were proposed, but testing them experimentally is a challenge, due to hardly accessible length scales and to the influence of regulatory proteins constantly changing the mechanical properties of polymerizing filaments. We present an experimental setup designed to minimize the number of parameters influencing filament growth to focus on the mechanism of force generation. We demonstrate that it is consistent with the Brownian ratchet model. Furthermore, we define a criterion for cell migration efficiency and quantify the number of filaments that need to push the membrane to maximize this efficiency.
(+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of
Plasmodium
Authors: Jiménez-Díaz María Belén , Ebert Daniel , Salinas Yandira , Pradhan Anupam , Lehane Adele M. , Myrand-Lapierre Marie-Eve , O’Loughlin Kathleen G. , Shackleford David M. , Justino de Almeida Mariana , Carrillo Angela K. , Clark Julie A. , Dennis Adelaide S. M. , Diep Jonathon , Deng Xiaoyan , Duffy Sandra , Endsley Aaron N. , Fedewa Greg , Guiguemde W. Armand , Gómez María G. , Holbrook Gloria , Horst Jeremy , Kim Charles C. , Liu Jian , Lee Marcus C. S. , Matheny Amy , Martínez María Santos , Miller Gregory , Rodríguez-Alejandre Ane , Sanz Laura , Sigal Martina , Spillman Natalie J. , Stein Philip D. , Wang Zheng , Zhu Fangyi , Waterson David , Knapp Spencer , Shelat Anang , Avery Vicky M. , Fidock David A. , Gamo Francisco-Javier , Charman Susan A. , Mirsalis Jon C. , Ma Hongshen , Ferrer Santiago , Kirk Kiaran , Angulo-Barturen Iñigo , Kyle Dennis E. , DeRisi Joseph L. , Floyd David M. , Guy R. Kiplin
Published: December 2014

Significance

Useful antimalarial drugs must be rapidly acting, highly efficacious, and have low potential for developing resistance. (+)-SJ733 targets a
Plasmodium
cation-transporting ATPase, ATP4. (+)-SJ733 cleared parasites in vivo as quickly as artesunate by specifically inducing eryptosis/senescence in infected, treated erythrocytes. Although in vitro selection of
pfatp4
mutants with (+)-SJ733 proceeded with moderate frequency, during in vivo selection of
pbatp4
mutants, resistance emerged slowly and produced marginally resistant mutants with poor fitness. In addition, (+)-SJ733 met all other criteria for a clinical candidate, including high oral bioavailability, a high safety margin, and transmission blocking activity. These results demonstrate that targeting ATP4 has great potential to deliver useful drugs for malaria eradication.
hERG 1b is critical for human cardiac repolarization
Authors: Jones David K. , Liu Fang , Vaidyanathan Ravi , Eckhardt L. Lee , Trudeau Matthew C. , Robertson Gail A.
Published: December 2014

Significance

The 1a subunit of the human ether-à-go-go–related gene (hERG) potassium channel is a critical component of cardiac repolarization and the cornerstone of safety screens for new drug development. A second subunit, 1b, coassembles with 1a and modifies channel gating and drug block sensitivity. Adoption of 1a/1b heteromers as a model of native hERG current, I
Kr
, has been hampered by the absence of direct evidence that 1b contributes to human cardiac repolarization. This study provides the first functional evidence, to our knowledge, that 1a/1b channels rather than homomeric 1a channels mediate repolarization. Because heteromeric and homomeric hERG channels have different pharmacological profiles, these findings have implications for native I
Kr
models and hERG-based drug safety tests that help protect against drug-induced sudden cardiac death.
Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies
Authors: Kabanova Anna , Perez Laurent , Lilleri Daniele , Marcandalli Jessica , Agatic Gloria , Becattini Simone , Preite Silvia , Fuschillo Dario , Percivalle Elena , Sallusto Federica , Gerna Giuseppe , Corti Davide , Lanzavecchia Antonio
Published: December 2014

Significance

To design an effective subunit vaccine, it is essential to identify the most relevant protective antigen. One way to achieve this goal is to analyze, at the clonal level, the human antibody response and identify the molecules targeted by the most effective neutralizing antibodies. Here we provide an example of this approach in the case of human cytomegalovirus (HCMV), a pathogen causing severe disease in newborns and immunosuppressed individuals. Through the analysis of the human antibody response to HCMV, we identified the gHgLpUL128L pentamer as the target of the most potent neutralizing antibodies and demonstrated that a pentamer vaccine elicited in mice extremely high levels of HCMV neutralizing antibodies. This example illustrates a general approach to develop subunit vaccines against complex pathogens.
Toward resolving the catalytic mechanism of dihydrofolate reductase using neutron and ultrahigh-resolution X-ray crystallography
Authors: Wan Qun , Bennett Brad C. , Wilson Mark A. , Kovalevsky Andrey , Langan Paul , Howell Elizabeth E. , Dealwis Chris
Published: December 2014

Significance

There is immense difficulty in mapping out the complete details of an enzyme’s mechanism, especially those that catalyze an acid-base reaction, owing to the simple fact that hydrogen atom positions are rarely known with any confidence. Ultrahigh-resolution X-ray and, better still, neutron crystallography can provide this crucial layer of information. We paired these techniques to reveal the catalytic mechanism of dihydrofolate reductase (DHFR), an enzyme necessary for nucleotide biosynthesis and a classical drug target. In a complex that closely resembles the catalytically active state, DHFR stabilizes a particular substrate conformer and likely elevates the p
K
a
of the substrate atom that is protonated. This protonation occurs directly via water, with its access to the substrate regulated by structural fluctuation of the enzyme.
American mastodon extirpation in the Arctic and Subarctic predates human colonization and terminal Pleistocene climate change
Authors: Zazula Grant D. , MacPhee Ross D. E. , Metcalfe Jessica Z. , Reyes Alberto V. , Brock Fiona , Druckenmiller Patrick S. , Groves Pamela , Harington C. Richard , Hodgins Gregory W. L. , Kunz Michael L. , Longstaffe Fred J. , Mann Daniel H. , McDonald H. Gregory , Nalawade-Chavan Shweta , Southon John R.
Published: December 2014

Significance

New radiocarbon (14C) dates on American mastodon (Mammut americanum) fossils in Alaska and Yukon suggest this species suffered local extirpation before terminal Pleistocene climate changes or human colonization. Mastodons occupied high latitudes during the Last Interglacial (∼125,000–75,000 y ago) when forests were established. Ecological changes during the Wisconsinan glaciation (∼75,000 y ago) led to habitat loss and population collapse. Thereafter, mastodons were limited to areas south of the continental ice sheets, where they ultimately died out ∼10,00014C years B.P. Extirpation of mastodons and some other megafaunal species in high latitudes was thus independent of their later extinction south of the ice. Rigorous pretreatment was crucial to removing contamination from fossils that originally yielded erroneously “young”14C dates.
Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior
Authors: Ryglewski Stefanie , Kadas Dimitrios , Hutchinson Katie , Schuetzler Natalie , Vonhoff Fernando , Duch Carsten
Published: December 2014

Significance

Approximately 100 billion neurons in our brain form 100 trillion synapses onto 100,000 miles of dendritic cable. Accordingly, dendritic defects are consistent anatomical correlates of numerous brain diseases, but specific causality remains unproven. Here we genetically remove dendrites inDrosophilamotoneurons, followed by analysis of functional outcomes. We find that dendrites are surprisingly dispensable for basic nervous system function and simple behavioral tasks. By contrast, highly complex dendritic architecture is required for adaptive refinement of sophisticated motor tasks that are vital for survival and reproduction. Here the degree of dendritic defect scales with the degree of performance deficit. We postulate that during evolution the maintenance of complex dendritic structure is under high selective pressure.
Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering
Authors: Wall Michael E. , Van Benschoten Andrew H. , Sauter Nicholas K. , Adams Paul D. , Fraser James S. , Terwilliger Thomas C.
Published: December 2014

Significance

A major challenge of protein crystallography is to accurately describe protein structure variations. Whereas Bragg peaks only yield a picture in which the variations are superimposed, diffuse X-ray scattering (diffraction between the peaks) reports on the way different atoms move together and can be used to increase the accuracy of models. We have performed a molecular-dynamics (MD) simulation of crystalline staphylococcal nuclease, yielding a rich picture of functionally important motions. This simulation is 100-fold longer than previous studies and yields reproducible calculations of diffuse intensity, overcoming a major challenge in the field. Experimental data support the MD models and indicate that diffuse scattering can be used both to validate and to improve MD simulations.
Label-free imaging of Schwann cell myelination by third harmonic generation microscopy
Authors: Lim Hyungsik , Sharoukhov Denis , Kassim Imran , Zhang Yanqing , Salzer James L. , Melendez-Vasquez Carmen V.
Published: December 2014

Significance

Myelin, a specialized membrane wrapping around the axon, is crucial for proper neuronal information processing. We describe a label-free imaging method, i.e., third harmonic generation microscopy (THGM), for visualization of Schwann cell myelination in live culture and ex vivo and in vivo tissue. THGM is capable of imaging compact myelin as well as non–compact subcellular domains, including nodal segments, Schmidt–Lanterman incisures, and Cajal bands, thus attractive for elucidating their functional roles; it also facilitates image-based morphometry, allowing the g-ratio of myelinated fibers to be measured in physiological conditions. The demonstrated capabilities of THGM are valuable for investigating the intricate interaction between axon and myelin-forming glial cell underlying formation and maintenance of myelin in the peripheral nervous system.
Local plant names reveal that enslaved Africans recognized substantial parts of the New World flora
Authors: van Andel Tinde R. , van ‘t Klooster Charlotte I. E. A. , Quiroz Diana , Towns Alexandra M. , Ruysschaert Sofie , van den Berg Margot
Published: December 2014

Significance

Enslaved Africans had to familiarize themselves with the American flora, which was largely alien to them, to survive. The process of species recognition, knowledge acquisition, and replacement has hardly been documented. We compared 2,350 Afro-Surinamese vernacular plant names with those vernacular plant names used in western Africa for botanically related taxa. Sixty-five percent of the Afro-Surinamese plant names contained European lexical elements, but among Maroons, descendants of escaped slaves, more than 40% of the vernaculars showed strong resemblance in sound, structure, and meaning to African plant names for related taxa. The greatest correspondence was found among plant names from Gabon and Angola, the main areas where the Dutch purchased their slaves. Our paper shows that Africans recognized substantial parts of the American flora.
p53 prevents neurodegeneration by regulating synaptic genes
Authors: Merlo Paola , Frost Bess , Peng Shouyong , Yang Yawei J. , Park Peter J. , Feany Mel
Published: December 2014

Significance

The transcription factor p53 plays a critical role in the cellular response to DNA damage and has thus been studied intensively in oncogenesis research. However, the role that p53 plays in the response of postmitotic neurons to cellular stress has received less attention. Here we describe an unexpected neuroprotective role for p53 in an in vivo model of tau-mediated neurodegeneration relevant to Alzheimer's disease and related disorders. Further, we identify synaptic function as a novel target pathway for p53 in aging neurons, consistent with the growing evidence for synaptic pathology as an early event in neurodegenerative disease. Our study defines mechanistically a new, conserved role for p53 in protecting postmitotic neurons from degeneration during aging and disease.
Stoichiometry and assembly of mTOR complexes revealed by single-molecule pulldown
Authors: Jain Ankur , Arauz Edwin , Aggarwal Vasudha , Ikon Nikita , Chen Jie , Ha Taekjip
Published: December 2014

Significance

The mammalian target of rapamycin (mTOR) kinase is a central regulator of cell growth, differentiation, and metabolism. mTOR is assembled into two distinct complexes, mTORC1 and mTORC2. Using single-molecule pulldown (SiMPull), we have determined the stoichiometric composition of mTORCs under growth and stress conditions. We find that both mTORC1 and mTORC2 form obligate dimers, in which major components exist in two copies per complex. Importantly, SiMPull allowed us to distinguish complex disassembly from stoichiometry changes, providing insights into the effects of physiological conditions and the drug rapamycin on mTOR complexes.
Direct interactions promote eviction of the Sir3 heterochromatin protein by the SWI/SNF chromatin remodeling enzyme
Authors: Manning Benjamin J. , Peterson Craig L.
Published: December 2014

Significance

Heterochromatin is a repressive mode of genetic storage that prevents cellular machineries from accessing DNA sequences. Here, we investigate how a protein machine, called SWI/SNF, can disrupt these heterochromatin structures and facilitate nuclear processes. We identify physical and functional interactions between SWI/SNF and a key heterochromatin protein, silent information regulator 3p (Sir3p).
Neuromolecular responses to social challenge: Common mechanisms across mouse, stickleback fish, and honey bee
Authors: Rittschof Clare C. , Bukhari Syed Abbas , Sloofman Laura G. , Troy Joseph M. , Caetano-Anollés Derek , Cash-Ahmed Amy , Kent Molly , Lu Xiaochen , Sanogo Yibayiri O. , Weisner Patricia A. , Zhang Huimin , Bell Alison M. , Ma Jian , Sinha Saurabh , Robinson Gene E. , Stubbs Lisa
Published: December 2014

Significance

In some cases similar molecular programs (i.e., conserved genes and gene networks) underlie the expression of phenotypic traits that evolve repeatedly across diverse species. We investigated this possibility in the context of social behavioral response, using a comparative genomics approach for three distantly related species: house mouse (
Mus musculus
), stickleback fish (
Gasterosteus aculeatus
), and honey bee (
Apis mellifera
). An experience of territory intrusion modulated similar brain functional processes across species, including hormone-mediated signal transduction, neurodevelopment, chromosome organization, and energy metabolism. Several homologous transcription factors also responded consistently to territory intrusion, suggesting that shared neuronal effects may involve transcriptional cascades of evolutionarily conserved genes. These results indicate that conserved genetic “toolkits” are involved in independent evolutions of social behavior.
Bisphosphonates inactivate human EGFRs to exert antitumor actions
Authors: Yuen Tony , Stachnik Agnes , Iqbal Jameel , Sgobba Miriam , Gupta Yogesh , Lu Ping , Colaianni Graziana , Ji Yaoting , Zhu Ling-Ling , Kim Se-Min , Li Jianhua , Liu Peng , Izadmehr Sudeh , Sangodkar Jaya , Bailey Jack , Latif Yathin , Mujtaba Shiraz , Epstein Solomon , Davies Terry F. , Bian Zhuan , Zallone Alberta , Aggarwal Aneel K. , Haider Shozeb , New Maria I. , Sun Li , Narla Goutham , Zaidi Mone
Published: December 2014

Significance

For over three decades, bisphosphonates have been used for the therapy of osteoporosis and skeletal metastasis. Here we show that this class of drugs reduces the viability of tumor cells that are driven by the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. We also show that bisphosphonates directly bind to and inhibit HER kinases. Because bisphosphonates are inexpensive and readily available worldwide, our findings may have important healthcare implications by offering an affordable and multiuse alternative or adjunct to current therapies for HER-driven malignancy.
RETRACTED: Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells
Authors: Samanta Debangshu , Gilkes Daniele M. , Chaturvedi Pallavi , Xiang Lisha , Semenza Gregg L.
Published: December 2014

Triple negative breast cancers (TNBCs) are defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 expression, and are treated with cytotoxic chemotherapy such as paclitaxel or gemcitabine, with a durable response rate of less than 20%. TNBCs are enriched for the basal subtype gene expression profile and the presence of breast cancer stem cells, which are endowed with self-renewing and tumor-initiating properties and resistance to chemotherapy. Hypoxia-inducible factors (HIFs) and their target gene products are highly active in TNBCs. Here, we demonstrate that HIF expression and transcriptional activity are induced by treatment of MDA-MB-231, SUM-149, and SUM-159, which are human TNBC cell lines, as well as MCF-7, which is an ER
+
/PR
+
breast cancer line, with paclitaxel or gemcitabine. Chemotherapy-induced HIF activity enriched the breast cancer stem cell population through interleukin-6 and interleukin-8 signaling and increased expression of multidrug resistance 1. Coadministration of HIF inhibitors overcame the resistance of breast cancer stem cells to paclitaxel or gemcitabine, both in vitro and in vivo, leading to tumor eradication. Increased expression of HIF-1α or HIF target genes in breast cancer biopsies was associated with decreased overall survival, particularly in patients with basal subtype tumors and those treated with chemotherapy alone. Based on these results, clinical trials are warranted to test whether treatment of patients with TNBC with a combination of cytotoxic chemotherapy and HIF inhibitors will improve patient survival.
Comparison of Tributary Survival Estimates of Steelhead using Cormack–Jolly–Seber and Barker Models: Implications for Sampling Efforts and Designs
Authors: Conner Mary M. , Bennett Stephen N. , Saunders W. Carl , Bouwes Nicolaas
Published: December 2014

We conducted simulations to compare the precision and bias of survival estimates from Cormack–Jolly–Seber (CJS) and Barker models to known parameter values based on empirical data for steelhead/resident Rainbow Trout Oncorhynchus mykiss from the John Day River, Oregon. We simulated seasonal differences in recapture and survival rates, and we varied the number of fish tagged, recapture and resight rates, sample site size, and fish movement (migratory or resident). Survival estimates from the Barker model had higher precision and lower or equal bias in comparison with estimates from the CJS model under almost all simulation scenarios. The precision of Barker survival estimates increased the most as the number of tagged fish increased from 50 to 200 (CV = 0.4–0.09). The Barker model's superior performance was dependent on the availability of resight data; such data are becoming more readily available, especially in places where large numbers of individuals are PIT‐tagged and where an interrogation infrastructure exists (e.g., Columbia River basin). Tagging of 75–100 fish/site during high‐capture periods (e.g., summer and fall) and focusing on the resighting of fish with fixed or mobile interrogators during low‐capture periods (i.e., winter and spring) may be the most cost‐effective strategy for improving estimates of juvenile steelhead survival.

Received April 18, 2014; accepted August 26, 2014
Fall Spawning of Atlantic Sturgeon in the Roanoke River, North Carolina
Authors: Smith Joseph A. , Flowers H. Jared , Hightower Joseph E.
Published: December 2014

In 2012, the National Oceanic and Atmospheric Administration (NOAA) declared Atlantic Sturgeon Acipenser oxyrinchus oxyrinchus to be threatened or endangered throughout its range in U.S. waters. Restoration of the subspecies will require much new information, particularly on the location and timing of spawning. We used a combination of acoustic telemetry and sampling with anchored artificial substrates (spawning pads) to detect fall (September–November) spawning in the Roanoke River in North Carolina. This population is included in the Carolina Distinct Population Segment, which was classified by NOAA as endangered. Sampling was done immediately below the first shoals encountered by anadromous fishes, near Weldon. Our collection of 38 eggs during the 21 d that spawning pads were deployed appears to be the first such collection (spring or fall) for wild‐spawned Atlantic Sturgeon eggs. Based on egg development stages, estimated spawning dates were September 17–18 and 18–19 at water temperatures from 25.3°C to 24.3°C and river discharge from 55 to 297 m3/s. These observations about fall spawning and habitat use should aid in protecting critical habitats and planning research on Atlantic Sturgeon spawning in other rivers.

Received April 14, 2014; accepted September 9, 2014
Ali Al-Wardi and his critique of the human mind
Authors: Al-Haidari Ibrahim
Published: December 2014

Ali Al-Wardi was influenced by the philosophical ideas that criticized the assumption that the nature of the human mind is fixed. These ideas come from his reading of Ibn Khaldun, Sigmund Freud and Karl Mannheim. He reinterpreted their ideas of the mind and applied it to Iraqi society and the Iraqi mind. He believes that human nature is egocentric and determined in most actions, motivated by the subconscious. The role of the mind is to justify human behaviour. The mind is one-sided and biased and is untrustworthy. It is only an organ that aids humans in their quest for survival. Also the mind has a limited capacity and is surrounded by a dense rim of values, beliefs and interests. Al-Wardi has launched a relentless campaign against the Aristotelian logic and against reason and rationality. Despite his rational analysis, he could not free himself from the mindset he identified as a farce and did not distinguish between the productive and the instrumental mind.
ITER-like current ramps in JET with ILW: experiments, modelling and consequences for ITER
Authors: Hogeweij G.M.D. , Calabrò G. , Sips A.C.C. , Maggi C.F. , De Tommasi G.M. , Joffrin E. , Loarte A. , Maviglia F. , Mlynar J. , Rimini F.G. , Pütterich Th.
Published: December 2014

Since the ITER-like wall in JET (JET-ILW) came into operation, dedicated ITER-like plasma current (I
p) ramp-up (RU) and ramp-down (RD) experiments have been performed and matched to similar discharges with the carbon wall (JET-C). The experiments show that access to H-mode early in the I
p RU phase and maintaining H-mode in the I
p RD as long as possible are instrumental to achieve low internal plasma inductance (l
i) and to minimize flux consumption. In JET-ILW, at a given current rise rate similar variations in l
i (0.7–0.9) are obtained as in JET-C. In most discharges no strong W accumulation is observed. However, in some low density cases during the early phase of the I
p

strong core radiation due to W influx led to hollow electron temperature (T
e) profiles. In JET-ILW Z
eff is significantly lower than in JET-C. W significantly disturbs the discharge evolution when the W concentration approaches 10−4; this threshold is confirmed by predictive transport modelling using the CRONOS code. I
p RD experiments in JET-ILW confirm the result of JET-C that sustained H-mode and elongation reduction are both instrumental in controlling l
i.
Mechanical Bowel Preparation for Children Undergoing Elective Colorectal Surgery
Authors: Aldrink Jennifer H. , McManaway Cindy , Wang Wei , Nwomeh Benedict C.
Published: December 2014

Objectives:

Adult literature supports the elimination of mechanical bowel preparation (MBP) for elective colorectal surgical procedures. Prospective data for the pediatric population regarding the utility of MBP are lacking. The primary aim of this study was to compare infectious complications, specifically anastomotic leak, intraabdominal abscess, and wound infection in patients who received MBP with those who did not.

Methods:

A randomized pilot study comparing MBP with polyethylene glycol with no MBP was performed. Patients, 0 to 21 years old, undergoing elective colorectal surgery were eligible and randomized within 4 age strata. Statistical analyses were performed using χ2 or Fisher exact test for categorical data and t test or Wilcoxon 2‐sample test for continuous data.

Results:

Forty‐four patients were enrolled in the study from December 2010 to February 2013, of which 24 (55%) received MBP and 20 (45%) did not. Two patients (5%) had anastomotic leak, 4 (9%) had intraabdominal infection, and 7 (16%) had wound infections. The rate of anastomotic leak, intraabdominal abscess, and wound infection did not differ between the 2 groups.

Conclusions:

MBP for elective colorectal surgery in children does not affect the incidence of infectious complications. A larger multiinstitutional study is necessary to validate the results of this single‐institution pilot study.
A novel role for the Pol I transcription factor UBTF in maintaining genome stability through the regulation of highly transcribed Pol II genes
Authors: Sanij Elaine , Diesch Jeannine , Lesmana Analia , Poortinga Gretchen , Hein Nadine , Lidgerwood Grace , Cameron Donald P. , Ellul Jason , Goodall Gregory J. , Wong Lee H. , Dhillon Amardeep S. , Hamdane Nourdine , Rothblum Lawrence I. , Pearson Richard B. , Haviv Izhak , Moss Tom , Hannan Ross D.
Published: December 2014

Mechanisms to coordinate programs of highly transcribed genes required for cellular homeostasis and growth are unclear. Upstream binding transcription factor (UBTF, also called UBF) is thought to function exclusively in RNA polymerase I (Pol I)-specific transcription of the ribosomal genes. Here, we report that the two isoforms of UBTF (UBTF1/2) are also enriched at highly expressed Pol II-transcribed genes throughout the mouse genome. Further analysis of UBTF1/2 DNA binding in immortalized human epithelial cells and their isogenically matched transformed counterparts reveals an additional repertoire of UBTF1/2-bound genes involved in the regulation of cell cycle checkpoints and DNA damage response. As proof of a functional role for UBTF1/2 in regulating Pol II transcription, we demonstrate that UBTF1/2 is required for recruiting Pol II to the highly transcribed histone gene clusters and for their optimal expression. Intriguingly, lack of UBTF1/2 does not affect chromatin marks or nucleosome density at histone genes. Instead, it results in increased accessibility of the histone promoters and transcribed regions to micrococcal nuclease, implicating UBTF1/2 in mediating DNA accessibility. Unexpectedly, UBTF2, which does not function in Pol I transcription, is sufficient to regulate histone gene expression in the absence of UBTF1. Moreover, depletion of UBTF1/2 and subsequent reduction in histone gene expression is associated with DNA damage and genomic instability independent of Pol I transcription. Thus, we have uncovered a novel role for UBTF1 and UBTF2 in maintaining genome stability through coordinating the expression of highly transcribed Pol I (UBTF1 activity) and Pol II genes (UBTF2 activity).
Iron-Binding E3 Ligase Mediates Iron Response in Plants by Targeting Basic Helix-Loop-Helix Transcription Factors
Authors: Selote Devarshi , Samira Rozalynne , Matthiadis Anna , Gillikin Jeffrey W. , Long Terri A.
Published: December 2014

Iron uptake and metabolism are tightly regulated in both plants and animals. In Arabidopsis (Arabidopsis thaliana), BRUTUS (BTS), which contains three hemerythrin (HHE) domains and a Really Interesting New Gene (RING) domain, interacts with basic helix-loop-helix transcription factors that are capable of forming heterodimers with POPEYE (PYE), a positive regulator of the iron deficiency response. BTS has been shown to have E3 ligase capacity and to play a role in root growth, rhizosphere acidification, and iron reductase activity in response to iron deprivation. To further characterize the function of this protein, we examined the expression pattern of recombinant ProBTS::β-GLUCURONIDASE and found that it is expressed in developing embryos and other reproductive tissues, corresponding with its apparent role in reproductive growth and development. Our findings also indicate that the interactions between BTS and PYE-like (PYEL) basic helix-loop-helix transcription factors occur within the nucleus and are dependent on the presence of the RING domain. We provide evidence that BTS facilitates 26S proteasome-mediated degradation of PYEL proteins in the absence of iron. We also determined that, upon binding iron at the HHE domains, BTS is destabilized and that this destabilization relies on specific residues within the HHE domains. This study reveals an important and unique mechanism for plant iron homeostasis whereby an E3 ubiquitin ligase may posttranslationally control components of the transcriptional regulatory network involved in the iron deficiency response.
Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples
Authors: Dullin Christian , dal Monego Simeone , Larsson Emanuel , Mohammadi Sara , Krenkel Martin , Garrovo Chiara , Biffi Stefania , Lorenzon Andrea , Markus Andrea , Napp Joanna , Salditt Tim , Accardo Agostino , Alves Frauke , Tromba Giuliana
Published: December 2014

Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were keptin situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites.
Data to knowledge: how to get meaning from your result
Authors: Berman Helen M. , Gabanyi Margaret J. , Groom Colin R. , Johnson John E. , Murshudov Garib N. , Nicholls Robert A. , Reddy Vijay , Schwede Torsten , Zimmerman Matthew D. , Westbrook John , Minor Wladek
Published: December 2014

Structural and functional studies require the development of sophisticated `Big Data' technologies and software to increase the knowledge derived and ensure reproducibility of the data. This paper presents summaries of the Structural Biology Knowledge Base, the VIPERdb Virus Structure Database, evaluation of homology modeling by the Protein Model Portal, theProSMARTtool for conformation-independent structure comparison, theLabDB`super' laboratory information management system and the Cambridge Structural Database. These techniques and technologies represent important tools for the transformation of crystallographic data into knowledge and information, in an effort to address the problem of non-reproducibility of experimental results.
Crystal structure of (E)-1-(4′-methoxy-[1,1′-biphenyl]-4-yl)-3-(3-nitrophenyl)prop-2-en-1-one
Authors: Vidhyasagar T. , Rajeswari K. , Shanthi D. , Kayalvizhi M. , Vasuki G. , Thiruvalluvar A.
Published: December 2014

The title compound, C22H17NO4, crystallizes with two independent molecules (AandB) in the asymmetric unit. Each molecule exists as anEisomer with C—C=C—C torsion angles of −175.69 (17) and −178.41 (17)° inAandB, respectively. In moleculeA, the planes of the terminal benzene rings are twisted by an angle of 26.67 (10)°, while the biphenyl unit is non-planar, the dihedral angle between the rings being 30.81 (10)°. The dihedral angle between the nitrophenyl ring and the inner phenyl ring is 6.50 (9)°. The corresponding values in moleculeBare 60.61 (9), 31.07 (8) and 31.05 (9)°. In the crystal, molecules are arranged in a head-to-head manner, with the 3-nitrophenyl groups nearly parallel to one another. TheAandBmolecules are linked to one anotherviaC—H...O hydrogen bonds, forming chains lying parallel to (-320) and enclosingR22(10) andR22(12) ring motifs. The methoxy group in both molecules is positionally disordered with a refined occupancy ratio of 0.979 (4):0.021 (4) for moleculeAand 0.55 (4):0.45 (4) for moleculeB.
Crystal structure of 1-methanesulfonyl-1,2,3,4-tetrahydroquinoline
Authors: Jeyaseelan S. , Nagendra Babu S. L. , Venkateshappa G. , Raghavendra Kumar P. , Palakshamurthy B. S.
Published: December 2014

In the title compound, C10H13NO2S, the heterocyclic ring adopts a half-chair conformation and the bond-angle sum at the N atom is 347.9°. In the crystal, inversion dimers linked by pairs of C—H...O hydrogen bonds generateR22(8) loops.
Crystal structure of ethyl 2-[2-((1E)-{(1E)-2-[2-(2-ethoxy-2-oxoethoxy)benzylidene]hydrazin-1-ylidene}methyl)phenoxy]acetate
Authors: Mague Joel T. , Mohamed Shaaban K. , Akkurt Mehmet , Ahmed Eman A. , Omran Omran A.
Published: December 2014

The complete molecule of the title compound, C22H24N2O6, is generated by crystallographic inversion symmetry and is approximately planar (r.m.s. deviation of the non-H atoms = 0.134 Å). The packing consists of inter-digitated sheets inclined at 25.9 (4)° to one another and linked by short C—H...O hydrogen bonds.
Crystal structure of cyprodinil
Authors: Jeon Youngeun , Kang Gihaeng , Cho Seonghwa , Kim Tae Ho
Published: December 2014

In the title compound, C14H15N3(systematic name: 4-cyclopropyl-6-methyl-N-phenylpyrimidin-2-amine), which is the anilinopyrimidine fungicide cyprodinil, the dihedral angles between the planes of the central pyrimidine ring and the terminal phenyl ring and the mean plane of the cyclopropane ring system are 14.52 (11) and 88.79 (10)°, respectively. In the crystal, weak π–π interactions [3.8551 (11) Å] connect the dimers into chains along theb-axis direction.
Crystal structure of 1,7,8,9-tetrachloro-4-(3,5-dichlorobenzyl)-10,10-dimethoxy-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione
Authors: Liu He , Zhong Jia-liang , Sun Wen-xia , Gong Yan-qing , Liu Li-hong
Published: December 2014

In the title compound, C17H11Cl6NO4, the configuration of the cycloalkene skeleton isendo,cis. The benzene ring is twisted by 58.94 (8)° from the attached pyrrolidine ring. Two carbonyl groups play a key role in the crystal packing. A short intermolecular C...O distance of 3.017 (3) Å reveals that one carbonyl group is involved in dipole–dipole interactions, which link two adjacent enantiomers into an inversion dimer. Another carbonyl group provides an acceptor for the weak intermolecular C—H...O hydrogen bonds which link these dimers into layers parallel to (011).
Crystal structure of 2-(1,3-dioxoindan-2-yl)isoquinoline-1,3,4-trione
Authors: Ghalib Raza Murad , Chidan Kumar C. S. , Hashim Rokiah , Sulaiman Othman , Fun Hoong-Kun
Published: December 2014

In the title isoquinoline-1,3,4-trione derivative, C18H9NO5, the five-membered ring of the indane fragment adopts an envelope conformation with the nitrogen-substituted C atom being the flap. The planes of the indane benzene ring and the isoquinoline-1,3,4-trione ring make a dihedral angle of 82.06 (6)°. In the crystal, molecules are linked into chains extending along thebcplaneviaC—H...O hydrogen-bonding interactions, enclosingR22(8) andR22(10) loops. The chains are further connected by π–π stacking interations, with centroid-to-centroid distances of 3.9050 (7) Å, forming layers parallel to thebaxis.
Crystal structure of (±)-(4RS,5RS,7SR)-4-[(1RS,2RS,3RS,6RS)-3-benzoyloxy-2-(2-hydroxyethyl)-6-methoxymethoxy-2-methylcyclohexyl]-8,10,10-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-8-en-7-yl benzoate benzene monosolvate
Authors: Oishi Takeshi , Yamaguchi Yuu , Fukaya Keisuke , Sugai Tomoya , Watanabe Ami , Sato Takaaki , Chida Noritaka
Published: December 2014

In the title compound, C36H44O10·C6H6, the dioxolane ring adopts an envelope conformation with the C atom bonded to the H atom as the flap, while the cyclohexene and cyclohexane rings are in half-chair and chair conformations, respectively. In the crystal, a pair of O—H...O hydrogen bonds with anR22(26) graph-set motif connect the benzoate molecules into an inversion dimer. The dimers are linked by a weak C—H...O interaction into a tape structure along [01-1]. The benzene molecule links the tapes through C—H...O and C—H...π interactions, forming a sheet parallel to (100).
Female anoles retain responsiveness to testosterone despite the evolution of androgen‐mediated sexual dimorphism
Authors: Cox Christian L. , Hanninen Amanda F. , Reedy Aaron M. , Cox Robert M.
Published: December 2014

The evolution of sexual dimorphism presents a challenge because males and females must express two phenotypes from the same underlying genome. In vertebrates, one solution to this challenge is to link the expression of shared traits to sex steroids. However, even ‘male‐biased’ steroids such as testosterone (T) circulate at biologically significant levels in females, raising the question of whether sexual dimorphism evolves not only through the coupling of trait expression to T in males, but also through the decoupling of trait expression from T in females.

We tested these alternatives by asking whether male and female brown anoles (Anolis sagrei) respond to exogenous T in similar fashion with respect to a suite of sexually dimorphic traits: growth, skeletal morphology, resting metabolism, fat storage, dewlap size and dewlap colour.

First, we established the ontogeny of sexual dimorphism in a colony raised in a laboratory common garden. Next, we treated juveniles of each sex with either T implants or empty implants at 5–8 months of age, when sexual dimorphism first began to develop for most traits.

T stimulated growth in both sexes and largely abolished natural sex differences in growth. This effect was associated with the stimulation of resting metabolism and the diversion of energy from fat and liver stores in both sexes. T also enlarged the dewlap in both sexes, though females never developed dewlaps equal in size to those of males. Finally, T altered the brightness and saturation of the dewlap in both sexes, inducing coloration similar to that of adult males.

Female brown anoles retain many of the same tissue‐specific responses to T that occur in males, suggesting that the evolution of androgen‐mediated sexual dimorphism has been achieved largely through the coupling of trait expression to sex differences in circulating T, without an associated decoupling of trait expression from T in females.
Uneven Natural Hedge Effects in the Wheat Sector and Implications for Risk Management Tools
Authors: Feng Siyi , Patton Myles , Binfield Julian , Davis John
Published: December 2014

Risk management tools have risen up the EU agricultural policy agenda in recent years due to greater market volatility. Market mechanisms can provide a natural hedge effect that moderates variability in revenue and income but not all regions benefit from this effect to the same extent. Core producing regions tend to benefit more while peripheral producing regions with dissimilar weather conditions benefit relatively little. We quantify the strength of natural hedge effects in the EU soft wheat sector. The two largest producing countries – France and Germany – have highly positively correlated yields and production thus driving EU wheat price changes. Our simulation shows that this hedge effect moderates revenue variability in these two countries by more than a third compared to price variability when crop yield is the only uncertainty source. By contrast, revenue variability in peripheral producing regions is consistently larger than price variability. This implies that there is a greater need for risk management tools in peripheral producing regions than in the core ones. The need for risk management tools is strongly linked to market conditions and so it is imperative that local characteristics are adequately considered if the over‐arching risk management policy framework is to be designed and set up at the EU level.
Why a European Agricultural Insurance Scheme is Not a Good Solution
Authors: Azcárate Tomás García
Published: December 2014

Would a European agricultural insurance scheme make sense today? My answer is not really. Even if we believe that weather‐related incidents will be even more likely as a consequence of climate change, representing a significant European challenge, in my view a decentralised approach to insurance is more suited to European agricultural diversities. In addition, an EU scheme would be expensive, financed through the budget discipline, resulting in a significant cut in direct payments. I present a first estimation of potential underlying costs that imply significant budget transfers from some west, north and central European Member States to Member States in south and east Europe. The difficulties, therefore, of finding enough political support for the proposal are obvious. This does not mean that nothing can be done. Already harvest insurance is eligible for EU support in the fruit, vegetable and wine sectors and state aids may also contribute to addressing adverse events. The CAP post‐2014 has introduced a risk management toolkit as a new measure in the Rural Development regulation but we should not be too optimistic about the prominence it will assume in national programming.