bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal intestinal HIF-2α is necessary for sensing iron demands of lactation in mice
Authors: Ramakrishnan Sadeesh K. , Anderson Erik R. , Martin Angelical , Centofanti Brook , Shah Yatrik M.
Published: June 2015

Significance

The benefits of breast milk in neonatal development are well characterized. However, very little is known about the essential nutrient components in breast milk that are critical for neonatal development and how these nutrients are maintained at adequate levels in breast milk. The present work demonstrates that the intestine is an essential sensor of systemic iron demand during lactation. During high iron demand from lactation, hypoxia-inducible factor-2α–mediated increase in maternal intestinal iron absorption is essential to maintain milk iron levels. This work demonstrates the significant role of maternal intestinal iron absorption in postnatal iron homeostasis of newborns and provides a therapeutic target to maintain iron homeostasis during pregnancy and lactation in anemic patients who are refractory to iron supplementation.
Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice
Authors: Yuan Chen-Ching , Muthu Priya , Kazmierczak Katarzyna , Liang Jingsheng , Huang Wenrui , Irving Thomas C. , Kanashiro-Takeuchi Rosemeire M. , Hare Joshua M. , Szczesna-Cordary Danuta
Published: June 2015

Significance

Genetic hypertrophic cardiomyopathy (HCM) is a debilitating disease affecting 1 in 500 of the general population, and there is no effective therapy to reverse or prevent its development and/or progression to heart failure. To inhibit a detrimental HCM phenotype induced by the D166V mutation of cardiac myosin regulatory light chain (RLC) in mice that also show reduced phosphorylation of endogenous cardiac RLC, constitutively phosphorylated D166V mutant mice were produced and tested. Our in-depth investigation of heart morphology, structure, and function of S15D-D166V mice provided evidence for the pseudophosphorylation-elicited prevention of the progressive HCM-D166V phenotype. This study is significant for the field of HCM, and our findings may constitute a novel therapeutic modality to battle hypertrophic cardiomyopathy associated with RLC mutations.
Arabidopsis
MZT1 homologs GIP1 and GIP2 are essential for centromere architecture
Authors: Batzenschlager Morgane , Lermontova Inna , Schubert Veit , Fuchs Jörg , Berr Alexandre , Koini Maria A. , Houlné Guy , Herzog Etienne , Rutten Twan , Alioua Abdelmalek , Fransz Paul , Schmit Anne-Catherine , Chabouté Marie-Edith
Published: June 2015

Significance

Centromeres are crucial as they avoid genomic instability during mitosis, but the mechanisms involved in their assembly and maintenance are not yet fully elucidated in eukaryotes. Here, we describe a previously unidentified aspect of centromere regulation mediated by γ-tubulin complex protein 3-interacting proteins (GIPs). Our data correlate centromere assembly and cohesion through the recruitment of specific protein complexes in the nucleus. Due to the conservation of GIPs/mitotic spindle organizing protein 1 among fungi, mammals, and plants, our results open a new field of investigation for centromere regulation.
Hydrodynamic collective effects of active protein machines in solution and lipid bilayers
Authors: Mikhailov Alexander S. , Kapral Raymond
Published: June 2015

Significance

Biological cells contain large numbers of active proteins that repeatedly change their conformations and need a supply of ATP or other substrates to maintain their cyclic operation. Whereas these protein machines have a variety of specific functions, acting as motors, ion pumps, or enzymes, they also induce fluctuating hydrodynamic flows in the cytoplasm. Because such fluctuating flows are nonthermal, energy can be extracted from them and work can be performed. We show that these flows can substantially enhance diffusive motions of passive particles. Furthermore, when gradients in concentrations of active proteins or substrate (ATP) are present, a chemotaxis-like drift should take place. Such nonequilibrium effects are universal: They hold for all passive particles and also for the protein machines themselves.
High-fat diet and FGF21 cooperatively promote aerobic thermogenesis in mtDNA mutator mice
Authors: Wall Christopher E. , Whyte Jamie , Suh Jae M. , Fan Weiwei , Collins Brett , Liddle Christopher , Yu Ruth T. , Atkins Annette R. , Naviaux Jane C. , Li Kefeng , Bright Andrew Taylor , Alaynick William A. , Downes Michael , Naviaux Robert K. , Evans Ronald M.
Published: June 2015

Significance

Fibroblast growth factor 21 (FGF21), a hormone that mediates an adaptive response to starvation, is also a long-standing marker of mitochondrial disease. In this article, we describe the metabolic benefits induced by mild mitochondrial stress via FGF21 induction in polymerase gamma mtDNA mutator (POLG) mice, a model of mitochondrial disease and premature aging. When challenged with a high-fat diet (HFD), these mice resist diet-induced obesity and its underlying associated disease states. In addition, nutrients from a HFD appear to reverse metabolic imbalance in these mice. HFD also robustly increases fat metabolism and improves mitochondrial function in brown fat, which mediates adaptive thermogenesis. Hence, we highlight a metabolically favorable synergy between mitochondrial stress and HFD facilitated by FGF21 in this mouse.
Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer’s disease amyloid plaques
Authors: Gowrishankar Swetha , Yuan Peng , Wu Yumei , Schrag Matthew , Paradise Summer , Grutzendler Jaime , De Camilli Pietro , Ferguson Shawn M.
Published: June 2015

Significance

Amyloid plaques, a key feature of Alzheimer’s disease brain pathology, comprise an extracellular β-amyloid core surrounded by tissue enriched in lysosome-like organelles. As a foundation for understanding the mechanisms that drive amyloid plaque formation, we have elucidated the cellular origins and molecular composition of such organelles. The majority of the lysosomes at amyloid plaques reside within swollen neuronal axons. Interestingly, these organelles contain low levels of multiple luminal lysosomal proteases and closely resemble a lysosome subpopulation that naturally occurs in distal neuronal processes. These results suggest that extracellular β-amyloid deposits cause a local impairment in retrograde axonal transport, leading to the accumulation of lysosome precursors and a blockade in their further maturation that has implications for both β-amyloid production and clearance.
Nature experience reduces rumination and subgenual prefrontal cortex activation
Authors: Bratman Gregory N. , Hamilton J. Paul , Hahn Kevin S. , Daily Gretchen C. , Gross James J.
Published: June 2015

Significance

More than 50% of people now live in urban areas. By 2050 this proportion will be 70%. Urbanization is associated with increased levels of mental illness, but it’s not yet clear why. Through a controlled experiment, we investigated whether nature experience would influence rumination (repetitive thought focused on negative aspects of the self), a known risk factor for mental illness. Participants who went on a 90-min walk through a natural environment reported lower levels of rumination and showed reduced neural activity in an area of the brain linked to risk for mental illness compared with those who walked through an urban environment. These results suggest that accessible natural areas may be vital for mental health in our rapidly urbanizing world.
F-box protein FBXO31 directs degradation of MDM2 to facilitate p53-mediated growth arrest following genotoxic stress
Authors: Malonia Sunil K. , Dutta Parul , Santra Manas Kumar , Green Michael R.
Published: June 2015

Significance

The tumor suppressor protein p53 plays a critical role in protecting humans from cancer. In response to cellular stresses, such as DNA damage, p53 levels increase and induce a variety of protective biological responses. In unstressed cells, p53 is maintained at a low level by MDM2, a protein that interacts with p53 and promotes its degradation. Following DNA damage, MDM2 is degraded rapidly, resulting in increased p53 levels. Because of the essential role of MDM2 in modulating p53 function, it is critical to understand how MDM2 levels are regulated. Here we show that, following DNA damage, the F-box protein FBXO31, a potential tumor suppressor, is responsible for promoting MDM2 degradation and therefore is essential for the increase in p53 levels.
Regulation of the plasma amino acid profile by leucine via the system L amino acid transporter
Authors: Zhen Hongmin , Nakamura Koichi , Kitaura Yasuyuki , Kadota Yoshihiro , Ishikawa Takuya , Kondo Yusuke , Xu Minjun , Shimomura Yoshiharu
Published: June 2015

Plasma concentrations of amino acids reflect the intracellular amino acid pool in mammals. However, the regulatory mechanism requires clarification. In this study, we examined the effect of leucine administration on plasma amino acid profiles in mice with and without the treatment of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) or rapamycin as an inhibitor of system L or mammalian target of rapamycin complex 1, respectively. The elevation of plasma leucine concentration after leucine administration was associated with a significant decrease in the plasma concentrations of isoleucine, valine, methionine, phenylalanine, and tyrosine; BCH treatment almost completely blocked the leucine-induced decrease in plasma amino acid concentrations. Rapamycin treatment had much less effects on the actions of leucine than BCH treatment. These results suggest that leucine regulates the plasma concentrations of branched-chain amino acids, methionine, phenylalanine, and tyrosine, and that system L amino acid transporters are involved in the leucine action.
CENP-C is a blueprint for constitutive centromere–associated network assembly within human kinetochores
Authors: Klare Kerstin , Weir John R. , Basilico Federica , Zimniak Tomasz , Massimiliano Lucia , Ludwigs Nina , Herzog Franz , Musacchio Andrea
Published: June 2015

Kinetochores are multisubunit complexes that assemble on centromeres to bind spindle microtubules and promote faithful chromosome segregation during cell division. A 16-subunit complex named the constitutive centromere–associated network (CCAN) creates the centromere–kinetochore interface. CENP-C, a CCAN subunit, is crucial for kinetochore assembly because it links centromeres with the microtubule-binding interface of kinetochores. The role of CENP-C in CCAN organization, on the other hand, had been incompletely understood. In this paper, we combined biochemical reconstitution and cellular investigations to unveil how CENP-C promotes kinetochore targeting of other CCAN subunits. The so-called PEST domain in the N-terminal half of CENP-C interacted directly with the four-subunit CCAN subcomplex CENP-HIKM. We identified crucial determinants of this interaction whose mutation prevented kinetochore localization of CENP-HIKM and of CENP-TW, another CCAN subcomplex. When considered together with previous observations, our data point to CENP-C as a blueprint for kinetochore assembly.
Cilia drop anchor
Authors: Leslie Mitch
Published: June 2015

Neurons use cilium’s transition zone to get a grip on surfaces.
Targeting phospholipase D1 attenuates intestinal tumorigenesis by controlling β-catenin signaling in cancer-initiating cells
Authors: Kang Dong Woo , Choi Chi Yeol , Cho Yong-Hee , Tian Huasong , Di Paolo Gilbert , Choi Kang-Yell , Min Do Sik
Published: June 2015

Expression of the Wnt target gene phospholipase D1 (PLD1) is up-regulated in various carcinomas, including colorectal cancer (CRC). However, the mechanistic significance of its elevated expression in intestinal tumorigenesis remains unknown. In this study, we show that genetic and pharmacological targeting of PLD1 disrupts spontaneous and colitis-associated intestinal tumorigenesis in ApcMin/+ and azoxymethane/dextran sodium sulfate mice models. Intestinal epithelial cell–specific PLD1 overexpression in ApcMin/+ mice accelerated tumorigenesis with increased proliferation and nuclear β-catenin levels compared with ApcMin/+ mice. Moreover, PLD1 inactivation suppressed the self-renewal capacity of colon cancer–initiating cells (CC-ICs) by decreasing expression of β-catenin via E2F1-induced microRNA (miR)-4496 up-regulation. Ultimately, low expression of PLD1 coupled with a low level of CC-IC markers was predictive of a good prognosis in CRC patients, suggesting in vivo relevance. Collectively, our data reveal that PLD1 has a crucial role in intestinal tumorigenesis via its modulation of the E2F1–miR-4496–β-catenin signaling pathway. Modulation of PLD1 expression and activity represents a promising therapeutic strategy for the treatment of intestinal tumorigenesis.
Effects of Germination Duration on Milling, Physicochemical, and Textural Properties of Medium‐ and Long‐Grain Rice
Authors: Han Ashley , Arijaje Emily O. , Jinn Jia‐Rong , Mauromoustakos Andy , Wang Ya‐Jane
Published: June 2015

Germinated brown rice is popular in Asia for its increased γ‐aminobutyric acid (GABA) content and sweeter and softer texture compared with conventional brown rice. However, most studies investigated germinated rice properties on medium‐grain or aromatic rice. The objective of this study was to compare differences between a medium‐grain (Jupiter) and a long‐grain (Wells) rice under similar germination conditions on their milling, physicochemical, and textural properties over the course of germination. Rough rice was soaked in water at 25°C for 12 h and then incubated at 30–34°C for four germination durations. Wells had a higher breakage percentage and a greater weight decrease than Jupiter during germination. Wells had a significantly lower GABA content before germination and at the first two germination durations than Jupiter, but the GABA content in Wells significantly increased at the third germination duration to become significantly higher than that of Jupiter. There were no significant changes in gelatinization temperatures and pasting properties of germinated rice from both cultivars at different germination durations. The cooked rice hardness from Wells decreased at the longest germination duration, whereas Jupiter showed a more significant decrease in cooked rice stickiness from germination. The results demonstrate that the impacts of germination on physical, chemical, and textural properties of rice were affected by grain type and germination duration.
Isolation and Partial Characterization of a Novel Cytorhabdovirus from Citrus Trees Showing Foliar Symptoms in Iran
Authors: Sadeghi Mohammad Sadegh , Afsharifar Alireza , Izadpanah Keramatollah , Loconsole Giuliana , De Stradis Angelo , Martelli Giovanni P. , Saponari Maria
Published: June 2015

Citrus ringspot is a graft-transmissible disease, and at least two taxonomically distinct viral species are associated with this syndrome: Citrus psorosis virus (CPsV) and Indian citrus ringspot virus (ICRSV). Neither of these two viruses was detected, however, by serological or molecular assays in symptomatic tissues from citrus trees in southern Iran, where the ringspot syndrome is widespread. By contrast, electron microscopy and molecular assays revealed the presence of a rhabdovirus-like virus, which was graft transmitted to several citrus species and mechanically to herbaceous hosts. Virus particles were bacilliform and resembled rhabdovirus nucleocapsids deprived of the lipoprotein envelope. Partial sequences of the viral nucleoprotein and RNA polymerase genes showed a distant genetic relatedness with cytorhabdoviruses. This virus appears to be a novel species, for which the name Iranian citrus ringspot-associated virus (IrCRSaV) is suggested.
Effects of Development of Ontogenic Resistance in Strawberry Leaves Upon Pre- and Postgermination Growth and Sporulation of Podosphaera aphanis
Authors: Asalf Belachew , Gadoury David M. , Tronsmo Anne Marte , Seem Robert C. , Stensvand Arne
Published: June 2015

The temporal distribution and magnitude of ontogenic resistance in strawberry leaves to Podosphaera aphanis has recently been quantified. However, the degree to which the pathogen is inhibited at sequential stages of conidial germination, hyphal growth, haustoria formation, latent period, colony expansion, and sporulation on the adaxial and abaxial leaf surfaces of various strawberry cultivars remains unclear. Five developmental stages of strawberry leaves ranging from newly emerged and folded leaves to fully expanded and dark-green leaves were inoculated with conidia of P. aphanis. The percentage of germinated conidia significantly declined between leaf stages 3 and 5. Postgermination growth of the pathogen was sequentially reduced in all measured responses, and the latent period was increased. Haustoria were not observed in mature leaves. The failure of the pathogen to penetrate mature leaves was a consistent feature associated with the expression of ontogenic resistance in older, fully expanded leaves.
Effects of Blueberry red ringspot virus on Yield and Fruit Maturation in Southern Highbush Blueberry
Authors: Williford L. A. , Savelle A. T. , Scherm H.
Published: June 2015

Blueberry red ringspot virus (BRRV) has become prevalent in southern highbush blueberry in the southeastern United States but information about the yield effects associated with the disease is limited and conflicting. A 3-year study was conducted on mature, container-grown plants of ‘Star’ and ‘Jewel’ blueberry that were either systemically infected or not infected with BRRV to determine the effect of the disease on flower bud numbers and fruit yield and on advances or delays in fruit ripening. On Star, flower bud counts were lower for BRRV-positive plants (P = 0.0137 in one year and P = 0.1085 in another) but no such effect was observed for Jewel. When fruit were harvested over time during the ripening period in the spring, no consistent yield or berry weight reductions were observed due to BRRV infection for either cultivar. On Star, fruit maturity tended to be slightly advanced in BRRV-positive plants in all years. Specifically, the weight of unripe fruit remaining after the last harvest was consistently lower for BRRV-positive plants than for BRRV-negative plants, suggesting that BRRV infection in Star may lead to a shorter fruit ripening period. No such effect on fruit ripening was observed for Jewel. It is concluded that—for the cultivars examined in this study—BRRV causes a relatively benign infection with no negative yield implications.
Management of Daylily Rust with Different Fungicide Combinations and Spray Intervals
Authors: Emmitt R. S. , Stevenson K. L. , Brenneman T. B. , Buck J. W.
Published: June 2015

Daylily (Hemerocallis spp.) is a popular herbaceous perennial plant and was considered to be relatively disease free until 2000, when daylily rust, caused by Puccinia hemerocallidis, was first detected in the United States. Management of daylily rust in nurseries is dependent on the use of fungicides, which are typically applied to the foliage of large blocks of plants at 21- or 28-day intervals. The objectives of this study were to determine the most effective fungicides or fungicide combinations and application intervals for managing daylily rust in the field. Foliar sprays of azoxystrobin alone at 14-, 21-, or 28-day intervals, combinations of azoxystrobin + propiconazole, azoxystrobin + chlorothalonil, propiconazole + chlorothalonil, and chlorothalonil + thiophanate-methyl applied at intervals of 21or 28 days, and a nontreated control were evaluated under high disease pressure, at three locations in Griffin, GA in 2014. In all three fields, all treatments that included azoxystrobin were effective at reducing area under the disease progress curve (AUDPC) compared with the nontreated control. At two of the three locations, azoxystrobin applied at 14-day intervals had significantly lower AUDPC than when applied at 21- or 28-day intervals. The addition of propiconazole or chlorothalonil to azoxystrobin did not improve rust control. Disease ratings for propiconazole + chlorothalonil and thiophanate-methyl + chlorothalonil applied at 21- or 28-day intervals did not differ from the untreated control. The 21-day treatments resulted in significantly lower disease than 28-day treatments (all fungicides) in the middle and end of the season. Elimination of less efficacious active ingredients and unnecessary applications can help growers maximize profitability by reducing expenses as well as simplifying fungicide inventory and storage.
Rembrandt’s Ocular Pathologies
Authors: Wiser Itay , Parnass Adam J. , Rachmiel Ronny , Westreich Melvyn , Friedman Tali
Published: June 2015

Purpose:

This article aims to medically and artistically analyze various ophthalmological ailments documented in self-portraits of Rembrandt to determine if those ailments were medical conditions or stylistic and age-related changes.

Methods:

A systematic literature review using Pub Med and Google Scholar found 232 results from a search of “Rembrandt” and more than 5,000 results for “Rembrandt Aging.” After extensive review of the literature, the authors found 17 relevant sources. These sources were then supplemented with historical books on Rembrandt and the aging processes of artists. Analytical observations with proportional measurements of anthropometrical landmarks (from self-portraits of Rembrandt at various ages) were studied, measured, analyzed, and compared using a standardized technique via MB ruler graphic software to assess age- or medically related changes.

Results:

The ophthalmological problems cited in the literature related to Rembrandt’s periorbital structures were found by the authors to be false. Signs of inappropriate aging and ailments, such as hyperthyroidism were deemed inaccurate by the authors based on absence of classical disease progression. Ophthalmological problems cited in the literature on Rembrandt’s visual acuity were found to be stylistic changes or considered normal aging. Finally, the authors found that ophthalmological problems relating to Rembrandt’s eye and orbital adnexa are unfitting because these problems were not seen in subsequent paintings.

Conclusions:

The authors believe that all the physical changes seen in Rembrandt’s portraits represent natural age-related or stylistic changes, and do not represent signs or symptoms of diseases in the master.
Towards quantized number theory: spectral operators and an asymmetric criterion for the Riemann hypothesis
Authors: Lapidus Michel L.
Published: June 2015

This research expository article not only contains a survey of earlier work but also contains a main new result, which we first describe. Givenc≥0, the spectral operatorcan be thought of intuitively as the operator which sends the geometry onto the spectrum of a fractal string of dimension not exceedingc. Rigorously, it turns out to coincide with a suitable quantization of the Riemann zeta functionζ=ζ(s):, where ∂=∂cis the infinitesimal shift of the real line acting on the weighted Hilbert space. In this paper, we establish a new asymmetric criterion for the Riemann hypothesis (RH), expressed in terms of the invertibility of the spectral operator for all values of the dimension parameter(i.e. for allcin the left half of the critical interval (0,1)). This corresponds (conditionally) to a mathematical (and perhaps also, physical) ‘phase transition’ occurring in the midfractal case when. Both the universality and the non-universality ofζ=ζ(s) in the right (resp., left) critical strip(resp.,) play a key role in this context. These new results are presented here. We also briefly discuss earlier joint work on the complex dimensions of fractal strings, and we survey earlier related work of the author with Maier and with Herichi, respectively, in which were established symmetric criteria for the RH, expressed, respectively, in terms of a family of natural inverse spectral problems for fractal strings of Minkowski dimensionD∈(0,1), with, and of the quasi-invertibility of the family of spectral operators(with).
Bell's conspiracy, Schrödinger's black cat and global invariant sets
Authors: Palmer T. N.
Published: June 2015

A locally causal hidden-variable theory of quantum physics need not be constrained by the Bell inequalities if this theory also partially violates the measurement independence condition. However, such violation can appear unphysical, implying implausible conspiratorial correlations between the hidden variables of particles being measured and earlier determinants of instrumental settings. A novel physically plausible explanation for such correlations is proposed, based on the hypothesis that states of physical reality lie precisely on a non-computational measure-zero dynamically invariant set in the state space of the universe: the Cosmological Invariant Set Postulate. To illustrate the relevance of the concept of a global invariant set, a simple analogy is considered where a massive object is propelled into a black hole depending on the decay of a radioactive atom. It is claimed that a locally causal hidden-variable theory constrained by the Cosmological Invariant Set Postulate can violate the Clauser–Horne–Shimony–Holt inequality without being conspiratorial, superdeterministic, fine-tuned or retrocausal, and the theory readily accommodates the classical compatibilist notion of (experimenter) free will.
The power of single molecule real-time sequencing technology in the denovoassembly of a eukaryotic genome
Authors: Sakai Hiroaki , Naito Ken , Ogiso-Tanaka Eri , Takahashi Yu , Iseki Kohtaro , Muto Chiaki , Satou Kazuhito , Teruya Kuniko , Shiroma Akino , Shimoji Makiko , Hirano Takashi , Itoh Takeshi , Kaga Akito , Tomooka Norihiko
Published: June 2015

Second-generation sequencers (SGS) have been game-changing, achieving cost-effective whole genome sequencing in many non-model organisms. However, a large portion of the genomes still remains unassembled. We reconstructed azuki bean (Vigna angularis) genome using single molecule real-time (SMRT) sequencing technology and achieved the best contiguity and coverage among currently assembled legume crops. The SMRT-based assembly produced 100 times longer contigs with 100 times smaller amount of gaps compared to the SGS-based assemblies. A detailed comparison between the assemblies revealed that the SMRT-based assembly enabled a more comprehensive gene annotation than the SGS-based assemblies where thousands of genes were missing or fragmented. A chromosome-scale assembly was generated based on the high-density genetic map, covering 86% of the azuki bean genome. We demonstrated that SMRT technology, though still needed support of SGS data, achieved a near-complete assembly of a eukaryotic genome.
A simple method for automated equilibration detection in molecular simulations
Authors: Chodera John D.
Published: June 2015

Molecular simulations intended to compute equilibrium properties are often initiated from configurations that are highly atypical of equilibrium samples, a practice which can generate a distinct initial transient in mechanical observables computed from the simulation trajectory. Traditional practice in simulation data analysis recommends this initial portion be discarded toequilibration,but no simple, general, and automated procedure for this process exists. Here, we suggest a conceptually simple automated procedure that does not make strict assumptions about the distribution of the observable of interest, in which the equilibration time is chosen to maximize the number of effectively uncorrelated samples in the production timespan used to compute equilibrium averages. We present a simple Python reference implementation of this procedure, and demonstrate its utility on typical molecular simulation data.
Long term recordings with immobile silicon probes in the mouse cortex
Authors: Okun Michael , Carandini Matteo , Harris Kenneth D.
Published: June 2015

A key experimental approach in neuroscience involves measuring neuronal activity in behaving animals with extracellular chronic recordings. Such chronic recordings were initially made with single electrodes and tetrodes, and are now increasingly performed with high-density, high-count silicon probes. A common way to achieve long-term chronic recording is to attach the probes to microdrives that progressively advance them into the brain and isolate them from mechanical forces. Here we report, however, that such microdrives are not strictly necessary. Indeed, we obtained high-quality recordings in both head-fixed and freely moving mice for several months following the implantation of immobile chronic probes. Probes implanted into the primary visual cortex yielded well-isolated single units whose spike waveform and orientation tuning were highly reproducible over time. Although electrode drift was not completely absent, at least 70% of neurons retained their waveform across days. Thus, immobile silicon probes represent a straightforward and reliable technique to obtain stable, long-term population recordings in mice, and to follow the activity of populations of well-isolated neurons over multiple days.
Genome-wide analysis of translational efficiency reveals distinct but overlapping functions of yeast DEAD-box RNA helicases Ded1 and eIF4A
Authors: Sen Neelam Dabas , Zhou Fujun , Ingolia Nicholas T. , Hinnebusch Alan G.
Published: June 2015

DEAD-box RNA helicases eIF4A and Ded1 are believed to promote translation initiation by resolving mRNA secondary structures that impede ribosome attachment at the mRNA 5′ end or subsequent scanning of the 5′ UTR, but whether they perform unique or overlapping functions in vivo is poorly understood. We compared the effects of mutations in Ded1 or eIF4A on global translational efficiencies (TEs) in budding yeast Saccharomyces cerevisiae by ribosome footprint profiling. Despite similar reductions in bulk translation, inactivation of a cold-sensitive Ded1 mutant substantially reduced the TEs of >600 mRNAs, whereas inactivation of a temperature-sensitive eIF4A variant encoded by tif1-A79V (in a strain lacking the ortholog TIF2) yielded <40 similarly impaired mRNAs. The broader requirement for Ded1 did not reflect more pervasive secondary structures at low temperature, as inactivation of temperature-sensitive and cold-sensitive ded1 mutants gave highly correlated results. Interestingly, Ded1-dependent mRNAs exhibit greater than average 5′ UTR length and propensity for secondary structure, implicating Ded1 in scanning through structured 5′ UTRs. Reporter assays confirmed that cap-distal stem–loop insertions increase dependence on Ded1 but not eIF4A for efficient translation. While only a small fraction of mRNAs shows a heightened requirement for eIF4A, dependence on eIF4A is correlated with requirements for Ded1 and 5′ UTR features characteristic of Ded1-dependent mRNAs. Our findings suggest that Ded1 is critically required to promote scanning through secondary structures within 5′ UTRs, and while eIF4A cooperates with Ded1 in this function, it also promotes a step of initiation common to virtually all yeast mRNAs.
Protonation and geometry of histidine rings
Authors: Malinska Maura , Dauter Miroslawa , Kowiel Marcin , Jaskolski Mariusz , Dauter Zbigniew
Published: June 2015

The presence of H atoms connected to either or both of the two N atoms of the imidazole moiety in a histidine residue affects the geometry of the five-membered ring. Analysis of the imidazole moieties found in histidine residues of atomic resolution protein crystal structures in the Protein Data Bank (PDB), and in small-molecule structures retrieved from the Cambridge Structural Database (CSD), identified characteristic patterns of bond lengths and angles related to the protonation state of the imidazole moiety. Using discriminant analysis, two functions could be defined, corresponding to linear combinations of the four most sensitive stereochemical parameters, two bond lengths (ND1–CE1 and CE1–NE2) and two endocyclic angles (–ND1– and –NE2–), that uniquely identify the protonation states of all imidazole moieties in the CSD and can be used to predict which N atom(s) of the histidine side chains in protein structures are protonated. Updated geometrical restraint target values are proposed for differently protonated histidine side chains for use in macromolecular refinement.
Intercalating dyes for enhanced contrast in second-harmonic generation imaging of protein crystals
Authors: Newman Justin A. , Scarborough Nicole M. , Pogranichniy Nicholas R. , Shrestha Rashmi K. , Closser Richard G. , Das Chittaranjan , Simpson Garth J.
Published: June 2015

The second-harmonic generation (SHG) activity of protein crystals was found to be enhanced by up to ∼1000-fold by the intercalation of SHG phores within the crystal lattice. Unlike the intercalation of fluorophores, the SHG phores produced no significant background SHG from solvated dye or from dye intercalated into amorphous aggregates. The polarization-dependent SHG is consistent with the chromophores adopting the symmetry of the crystal lattice. In addition, the degree of enhancement for different symmetries of dyes is consistent with theoretical predictions based on the molecular nonlinear optical response. Kinetics studies indicate that intercalation arises over a timeframe of several minutes in lysozyme, with detectable enhancements within seconds. These results provide a potential means to increase the overall diversity of protein crystals and crystal sizes amenable to characterization by SHG microscopy.
“Robinhoodian” courts’ decisions on mortgage law in Spain
Authors: Nasarre-Aznar Sergio
Published: June 2015

Purpose

– The purpose of this paper is to examine the response of the Spanish courts to the effects of the 2007 financial crisis for residential mortgage borrowers in the absence of any equivalent intervention by the legislature. The paper also explores the potential risks that recent court decisions might pose for the Spanish mortgage and banking systems.

Design/methodology/approach

– The paper uses a combination of doctrinal and comparative methodology. It undertakes an analysis of decided judicial cases in Spain and compares these to international courts’ decisions and to national and international legislation with a view to exploring their originality in the field of mortgage-related consumer protection.

Findings

– The reviewed cases demonstrate the need to consider legislative reforms to increase the protection of consumers in relation to mortgages. Some reforms took place in 2013, but these were not perceived as sufficient by the judiciary. The paper also highlights the legal uncertainty that has followed these decisions and its negative impact on the credibility of the Spanish financial and legal systems.

Research limitations/implications

– The cases discussed are exceptional in the context of the general “normal” or “traditional” application of contractual, procedural and mortgage legislation by the rest of the judiciary. However, they are relevant enough to detect a trend and the need for the revision of affected statutes.

Originality/value

– This paper provides the first systematic critical analysis of these cases. It is of particular significance, as they collectively represent a distortion of the civil law principles that provide the basis of Spanish mortgage law and, therefore, of the wider financial system.
Incoherence and incompatibility in planning law
Authors: Lees Emma , Shepherd Edward
Published: June 2015

Purpose

– The purpose of this paper is to analyse the obligations imposing localism and the presumption in favour of sustainable development in English planning law.

Design/methodology/approach

– The paper uses doctrinal analysis to examine section 38 PCPA 2004 and the NPPF to assess whether the obligations are coherent when considered as stand-alone obligations, and whether they are compatible when combined. Case law and the statutory provisions are examined to assess this. Planning theory is also examined to bring a multidisciplinary focus to the analysis.

Findings

– The paper concludes that there are problems with these legal obligations when considered as stand-alone obligations. There is imprecision over the meaning of key terms; the “presumptions” established do not operate as true presumptions; and there is an ambiguity as to the hierarchy of norms and the allocation of decision-making control. When combined, the incoherence increases. It is argued that this occurs thanks to underlying disagreements in key concepts in planning theory.

Originality/value

– This paper examines the new structures of planning law introduced under the Localism Act 2011 and the NPPF and considers how this structure works in practice. It does so from the multidisciplinary viewpoint of planning law and planning theory and links these two approaches. This is not replicated elsewhere in the literature. It considers in detail the ensuing case law, and the contradictions that appear. Again, there is little surveying the overall framework of planning law in the UK.
Doing ethnography in a paranoid organization: an autoethnographic account
Authors: Frandsen Sanne
Published: June 2015

Purpose

– The purpose of this paper is to examine what we can learn from an autoethnographical approach about public administration. In this context it presents and discusses the advantages and disadvantages of autoethnography.

Design/methodology/approach

– The paper is based on a case study of E-rail, a European national rail service subject to extensive negative press coverage. The autoethnographic accounts, based on interviews, observations, phone calls, e-mails, and other informal interactions with the organizational members, highlight the researcher’s entry to and exit of the organization.

Findings

– The paper mobilizes fieldwork access negotiation and trust building with participants as empirical material in its own right, arguing that challenges involving “being in the field” should be explored to provide new types of knowledge about the organizational phenomenon under study – in this case the rise of organizational paranoia.

Originality/value

– This paper uses autoethnography, which is rare in public administration studies, and discusses the distinct features of autoethnography as an ethnographic approach to public organizations. It argues that autoethnographic accounts of fieldwork relationship highlight and challenge the boundaries of the kind of research questions we might ask – and the kind of answers we might provide – about public administration.
Who are we trying to impress?
Authors: Boswell John , Corbett Jack
Published: June 2015

Purpose

– Turning laborious ethnographic research into stylized argumentative prose for academic consumption is a painstaking craft. The purpose of this paper is to revisit this perennial issue, and extend a claim the authors have made elsewhere about the inevitably impressionistic, rather than the oft-claimed “systematic”, nature of this task.

Design/methodology/approach

– The authors draw and reflect on their own experiences of conducting and navigating across political science, ethnography and interpretation in order to justify and uphold the benefits of impressionism.

Findings

– The authors argue that the impressionistic account of writing up fieldwork has important implications for these diverse disciplinary terrains.

Originality/value

– The authors develop an argument as to how and why an appreciation of this craft’s impressionistic nature can affect how the authors go about creating, evaluating and ultimately thinking about ethnographic research in foreign disciplines like political science.
Street-level planning; the shifty nature of “local knowledge and practice”
Authors: Vohnsen Nina Holm
Published: June 2015

Purpose

– The purpose of this paper is to explore and problematizes one of the oft-cited reasons why the implementation of public policy and other development initiatives goes wrong – namely that there is a mismatch or antagonistic relationship between street-level worker’s decisions and priorities on the one hand and on the other hand the policy-makers’ or administrators’ directives and priorities.

Design/methodology/approach

– The paper builds on seven months of ethnographic fieldwork set in a Danish municipal unit which administered the sickness benefit legislation.

Findings

– Through the reading of an ethnographic example of implementation of labour market policy this paper suggests that when policy invariably is distorted at the administrative level it is not necessarily due to lack of will among street-level workers to comply with legislation or centrally devised directives but rather because: in practice, planning and implementation are concurrent processes that continuously feed into each other; and that the concerns and the “local knowledge and practice” that guide planning-implementation do not belong to individual people but are dynamic perspectives that individual people might take up in certain situations.

Originality/value

– This challenges conventional descriptions of street-level workers as a distinct group of people with distinctive concerns and attitudes to their work. The paper suggests instead the metaphor “vector of concern” to capture the way street-level workers’ changes of perspectives might cause interventions to disintegrate and evolve in potentially conflicting directions.
FINRA 2015 regulatory and examinations priorities
Authors: Wirig Matthew T.
Published: June 2015

Purpose

– To summarize the Financial Industry Regulatory Authority, Inc. (“FINRA”) 2015 Regulatory and Examinations Priorities Letter.

Design/methodology/approach

– Provides a brief summary of the general compliance and supervisory challenges described by FINRA. Highlights key sales practice concerns raised by FINRA. Briefly summarizes FINRA’s 2015 key financial and operational priorities. Summarizes FINRA market integrity focuses for 2015. Encourages firms to consider the FINRA 2015 regulatory and examination priorities alongside the Securities and Exchange Commission (the “SEC”) examination priorities for 2015 as they review their policies, procedures and business activities.

Findings

– FINRA’s 2015 Regulatory and Examinations Priorities Letter focuses on: key areas FINRA has observed contributing to member firm compliance and supervisory deficiencies, its observation of an increase in firms failing to file timely responses to information requests in connection with examinations and investigations, key sales practice issues, financial and operational issues, and market integrity matters.

Practical implications

– Firms should review these priorities alongside the SEC’s examination priorities for 2015. Where firms observe deficiencies in their own practices, adjustments should be made before they find themselves the subject of a FINRA or SEC investigation, examination or enforcement action.

Originality/value

– Practical explanation by experienced financial services lawyer.
SEC IM staff issues guidance update on mixed and shared funding
Authors: Robinson Keith T. , Church Kimberley
Published: June 2015

Purpose

– The article alerts investment companies and insurers of important SEC staff interpretive guidance regarding reliance on industry-standard exemptive relief.

Design/methodology/approach

– Current industry practices and the SEC staff’s guidance are summarized, followed by a brief discussion of the potential implications to insurance companies and investment companies.

Findings

– The SEC staff recognizes that the current approach to mixed and shared funding may be outdated, with the result that insurance companies and investment companies may be able to reduce compliance and regulatory burdens.

Practical implications

– It is still too soon to gauge industry reaction, but insurance companies and investment companies should monitor industry practices relating to mixed and shared funding to determine whether they need to obtain and comply with industry-standard exemptive relief.

Originality/value

– The SEC staff clearly recognizes that insurance companies issuing variable insurance contracts, and the funds that serve as their underlying investments, may be able to reduce compliance monitoring burdens and simplify their operations.
FINRA publishes its 2015 “Report on Cybersecurity Practices”
Authors: Kuhlman Richard , Kempf Jason
Published: June 2015

Purpose

– To summarize and comment on FINRA’s report on cybersecurity practices, published on February 4, 2015, which arose from its 2014 targeted examination of firms’ cybersecurity preparedness.

Design/methodology/approach

– Explains the implications of the FINRA report and general guidance FINRA provides and expects all firms to consider in connection with developing their respective cybersecurity programs in eight areas: governance and risk management for cybersecurity; cybersecurity risk assessment; technical controls; incident response planning; vendor management; staff training; cyber intelligence and information sharing; and cyber insurance.

Findings

– There is no doubt that cybersecurity is a key risk facing the financial services industry now. Accordingly, FINRA expects that firms will review the report and assess how the principles and effective practices provided therein could help build or improve cybersecurity readiness. The report reflects FINRA’s risk-management-based approach to cybersecurity issues, identifying principles and “effective practices” for member firms to consider, as opposed to decreeing specific requirements, policies or procedures.

Originality/value

– Expert guidance from experienced securities lawyers.
Identity under challenge
Authors: Nach Hamid
Published: June 2015

Purpose

– The purpose of this paper is to examine how people respond when their identity is challenged as they use computerized information systems in organizational settings. Using the critical realism perspective, the author built on the identity control theory and suggested a set of generative mechanisms that shed light on how individuals respond to the challenges that information technology (IT) poses to their identities when performing their jobs and how it affects their sense of self.

Design/methodology/approach

– The author conducted a field study in a Canadian health-care institution with the objective to examine how doctors and nurses coped with challenges posed by an Electronic Health Records system to their identities and how these systems shaped their identities. The author’s data are essentially qualitative. The author used retroduction as a mode off inference which combines both induction and deduction. The author hypothesized a set of identity mechanisms that are enacted as a response to a threat posed by IT in the work place. The author uses the evidence from the field study to verify the existence of these mechanisms and uncover new constructs and relationships that could enrich the understanding of the phenomenon.

Findings

– The results allowed to verify and provide an updated view of the proposed generative mechanisms that are triggered when identity is put to challenge by IT in the workplace. The identified mechanisms are, identity adjusting, IT threat neutralizing and emotion regulating. Their outcomes, which are, reinforced identity, redefined identity, ambivalent identity and anti-identity are much dependent on the availability and the breadth of personal and organizational resources people have at their disposal.

Originality/value

– The research offers a vantage point on how identities unfold in the course of interaction with technology. It contributes by providing empirically grounded mechanisms that shed light on how people response to threats posed by computerized information systems to identity and the various self-conceptions that ensue.