bluuebunny/crossref_metadata_2025_split huggingface dataset:
The molecular architecture of dihydropyrindine receptor/L-type Ca2+ channel complex
Authors: Hu Hongli , Wang Zhao , Wei Risheng , Fan Guizhen , Wang Qiongling , Zhang Kaiming , Yin Chang-Cheng 
Published: February 2015

AbstractDihydropyridine receptor (DHPR), an L-type Ca2+ channel complex, plays an essential role in muscle contraction, secretion, integration of synaptic input in neurons and synaptic transmission. The molecular architecture of DHPR complex remains elusive. Here we present a 15-Å resolution cryo-electron microscopy structure of the skeletal DHPR/L-type Ca2+ channel complex. The DHPR has an asymmetrical main body joined by a hook-like extension. The main body is composed of a “trapezoid” and a “tetrahedroid”. Homologous crystal structure docking and site-specific antibody labelling revealed that the α1 and α2 subunits are located in the “trapezoid” and the β subunit is located in the “tetrahedroid”. This structure revealed the molecular architecture of a eukaryotic Ca2+ channel complex. Furthermore, this structure provides structural insights into the key elements of DHPR involved in physical coupling with the RyR/Ca2+ release channel and shed light onto the mechanism of excitation-contraction coupling.
“It's Not Humanly Possible to Do Everything”: Perspectives on Intervention Decision-Making Processes of Parents of Children with Autism Spectrum Disorders
Authors: Finke Erinn , Drager Kathryn , Serpentine Elizabeth C. 
Published: February 2015

Purpose
The purpose of this investigation was to understand the decision-making processes used by parents of children with autism spectrum disorder (ASD) related to communication-based interventions.

Method
Qualitative interview methodology was used. Data were gathered through interviews. Each parent had a child with ASD who was at least four-years-old; lived with their child with ASD; had a child with ASD without functional speech for communication; and used at least two different communication interventions.

Results
Parents considered several sources of information for learning about interventions and provided various reasons to initiate and discontinue a communication intervention. Parents also discussed challenges introduced once opinions of the school individualized education program (IEP) team had to be considered.

Conclusions
Parents of children with ASD primarily use individual decision-making processes to select interventions. This discrepancy speaks to the need for parents and professionals to share a common “language” about interventions and the decision-making process.
Chromatic‐dispersion‐free transmission using time‐reversal optical parametric amplifier
Authors: Ou Haiyan , Zhang Chi , Xu Xing , Lam Edmund Y. , Wong Kenneth K.Y. 
Published: February 2015

A chromatic‐dispersion‐free transmission using a time‐reversal optical parametric amplifier (OPA) for 10 Gbit/s data over 25 km of standard single‐mode fibre is demonstrated. The time‐reversal was achieved using optical phase conjugation in the OPA. A pilot signal was first sent to estimate the optical channel, which would be reshaped by the OPA and then retransmitted with data through the same fibre. The dispersion is compensated automatically through the transmission. Experimental results showed that around 1 dB improvement can be obtained at a bit error rate of <10−9 compared to the traditional return‐to‐zero on–off keying link.
DC link voltage balancing approach for cascaded H‐bridge active rectifier based on selective harmonic elimination‐pulse width modulation
Authors: Moeini Amirhossein , Iman‐Eini Hossein , Marzoughi Alinaghi 
Published: February 2015

This study presents an improved voltage balancing strategy which can be employed on multilevel cascaded H‐bridge (CHB) rectifiers using low switching frequency. The proposed method balances the voltage of all DC links in a CHB rectifier to a predefined value, without increasing the number of switching transitions. The redundancy states which are available in the CHB rectifier to produce a voltage level are used to balance the DC links in each transition. Moreover, using the well‐known selective harmonic elimination‐pulse width modulation method, all current harmonic components up to 29th harmonic are eliminated in the three‐phase CHB rectifier, whereas the average switching frequency of each switch is limited to 150 Hz. The effectiveness and validity of the proposed strategy is verified by several simulations and experiments that are carried out on a 7‐level CHB rectifier.
Recent Development in N-Auxilixary-Assisted Intramolecular Amination for Amine Substrates
Authors: Zhao Yingsheng , Wang Chao , Han Jian 
Published: February 2015

Direct coupling of N–H with C–H has aroused great attention in the last decades; during which the directing-group-assisted intramolecular C–N bond formation via transition metal has been achieved significant progress. Herein, we highlight the recent development in the directing-group-assisted intramolecular amination for amine substrates to build the important N-containing heterocyclic compounds.1	Introduction2	Triflamide-Promoted Intramolecular Amination3	Picolinamide-Assisted Intramolecular Amination4	Palladium-Catalyzed Intramolecular Amination under Assistance of Oxalyl Amide5	Conclusion
Gustatory and metabolic perception of nutrient stress in
Drosophila
Authors: Linford Nancy J. , Ro Jennifer , Chung Brian Y. , Pletcher Scott D. 
Published: February 2015

Significance
Starvation induces a suite of costly behavioral and metabolic responses to maximize the possibility of finding a new nutrient source. It is therefore advantageous for an organism to switch out of the starvation state when food is encountered. How does an animal know when a food source is found and ultimate starvation is unlikely? This new work addresses this fundamental question, which is essential for broadening our understanding of how organisms interpret information from their environment to enact changes in complex behaviors and physiology. We describe an intriguing mechanism that combines information from both sensory and metabolic perception depending on the nutrient density in the food source.
In-cell SHAPE reveals that free 30S ribosome subunits are in the inactive state
Authors: McGinnis Jennifer L. , Liu Qi , Lavender Christopher A. , Devaraj Aishwarya , McClory Sean P. , Fredrick Kurt , Weeks Kevin M. 
Published: February 2015

Significance
It has been known for decades that purified small subunits of the ribosome can interconvert between active and inactive conformations in experiments performed under simplified conditions, but the physiological relevance of this switch has remained unclear. We probed the structure of ribosomal RNA in healthy living cells and discovered that stably assembled 30S subunits exist predominantly in the inactive conformation, with structural differences localized in the functionally important decoding region. Disrupting the ability to interconvert between active and inactive conformations compromised translation in cells. In-cell RNA structure probing supports a model in which “inactive” 30S subunits comprise an abundant in-cell state that regulates ribosome function.
Human language reveals a universal positivity bias
Authors: Dodds Peter Sheridan , Clark Eric M. , Desu Suma , Frank Morgan R. , Reagan Andrew J. , Williams Jake Ryland , Mitchell Lewis , Harris Kameron Decker , Kloumann Isabel M. , Bagrow James P. , Megerdoomian Karine , McMahon Matthew T. , Tivnan Brian F. , Danforth Christopher M. 
Published: February 2015

Significance
The most commonly used words of 24 corpora across 10 diverse human languages exhibit a clear positive bias, a big data confirmation of the Pollyanna hypothesis. The study’s findings are based on 5 million individual human scores and pave the way for the development of powerful language-based tools for measuring emotion.
The second laws of quantum thermodynamics
Authors: Brandão Fernando , Horodecki Michał , Ng Nelly , Oppenheim Jonathan , Wehner Stephanie 
Published: February 2015

Significance
In ordinary thermodynamics, transitions are governed by a single quantity–the free energy. Its monotonicity is a formulation of the second law. Here, we find that the second law for microscopic or highly correlated systems takes on a very different form than it does at the macroscopic scale, imposing not just one constraint on state transformations, but many. We find a family of quantum free energies which generalize the standard free energy, and can never increase. The ordinary second law corresponds to the nonincreasing of one of these free energies, with the remainder imposing additional constraints on thermodynamic transitions. In the thermodynamic limit, these additional second laws become equivalent to the standard one. We also prove a strengthened version of the zeroth law of thermodynamics, allowing a definition of temperature.
Bacterial chemoreceptor dynamics correlate with activity state and are coupled over long distances
Authors: Samanta Dipanjan , Borbat Peter P. , Dzikovski Boris , Freed Jack H. , Crane Brian R. 
Published: February 2015

Significance
Bacterial chemoreceptors are a key system for understanding how conformational signals propagate over large distances in transmembrane signaling. We have applied pulsed dipolar ESR spectroscopy of spin-labeled receptors to correlate conformation and dynamics with activity state. We find that the receptor cytoplasmic domain behaves as one large dynamically coupled system, in which activation signals destabilize membrane proximal regions but stabilize the most distal protein interaction tip. Inhibitory signals or adaptations of the receptor through chemical modification produce the opposite changes in conformational properties. This reciprocal coupling of conformational stability provides a versatile mechanism for sending signals throughout large modular proteins.
Interplay of approximate planning strategies
Authors: Huys Quentin J. M. , Lally Níall , Faulkner Paul , Eshel Neir , Seifritz Erich , Gershman Samuel J. , Dayan Peter , Roiser Jonathan P. 
Published: February 2015

Significance
Many problems, particularly sequential planning problems, are computationally very demanding. How humans combine strategies to approximate and simplify these problems is not understood. Using modelling to unpick performance in a planning task, we find that humans are able to exploit the structure of the task to subdivide it and reduce processing requirements nearly optimally. Subtasks are combined in a simple, greedy manner, however, and within subtasks there is evidence of inhibitory reflexes in response to losses.
Erosion during extreme flood events dominates Holocene canyon evolution in northeast Iceland
Authors: Baynes Edwin R. C. , Attal Mikaël , Niedermann Samuel , Kirstein Linda A. , Dugmore Andrew J. , Naylor Mark 
Published: February 2015

Significance
The importance of high-magnitude, short-lived events in controlling the evolution of landscapes is not well understood. This matters because during such events, erosion processes can surpass thresholds and cause abrupt landscape changes that have a long-lasting legacy for landscape morphology. We show that extreme flood events, during which the flow depth exceeds the threshold for erosion through plucking rather than abrasion, are the dominant control on the evolution of a large bedrock canyon in Iceland. The erosive signature of these events is maintained within a dynamic landscape over millennial timescales, emphasizing the importance of episodic extreme events in shaping landscapes.
Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia
Authors: Yoshida Mayumi , Kataoka Naoyuki , Miyauchi Kenjyo , Ohe Kenji , Iida Kei , Yoshida Suguru , Nojima Takayuki , Okuno Yukiko , Onogi Hiroshi , Usui Tomomi , Takeuchi Akihide , Hosoya Takamitsu , Suzuki Tsutomu , Hagiwara Masatoshi 
Published: February 2015

Significance
Familial dysautonomia (FD) is caused by missplicing of the IκB kinase complex-associated protein (IKAP) gene, which results in the skipping of exon 20, especially in neurons. FD would be treatable if exon 20 inclusion were increased correctly to reestablish correct splicing. Here, we have established a dual-color splicing reporter that recapitulates FD-type splicing. By using this reporter, we have identified a small chemical compound, named rectifier of aberrant splicing (RECTAS), that rectifies the aberrant splicing of FD. RECTAS promotes both exon 20 inclusion and the product IKAP expression in cells of patients with FD. Furthermore, we have demonstrated that modification levels of wobble uridine residues of several tRNAs are reduced in FD cells and that RECTAS can recover not only tRNA modifications but also cell viability of FD cells.
Massively expedited genome-wide heritability analysis (MEGHA)
Authors: Ge Tian , Nichols Thomas E. , Lee Phil H. , Holmes Avram J. , Roffman Joshua L. , Buckner Randy L. , Sabuncu Mert R. , Smoller Jordan W. 
Published: February 2015

Significance
Practical tools for high-dimensional heritability-based screening are invaluable for prioritizing phenotypes for genetic studies with the dramatic expansion of available phenotypic data. Classical estimates of heritability require twin or pedigree data, which can be costly and difficult to acquire. Alternative methods based on whole-genome data from unrelated individuals exist but are computationally expensive. Here we present a novel, fast, and accurate statistical method for massively expedited genome-wide heritability analysis, making heritability-based prioritization of millions of phenotypes based on data from unrelated individuals tractable for the first time to our knowledge. We apply our method to large-scale heritability analyses of brain imaging measurements and demonstrate its potential for facilitating phenome-wide analyses and characterizing the genetic architecture of complex traits.
C-terminal sequence of amyloid-resistant type F apolipoprotein A-II inhibits amyloid fibril formation of apolipoprotein A-II in mice
Authors: Sawashita Jinko , Zhang Beiru , Hasegawa Kazuhiro , Mori Masayuki , Naiki Hironobu , Kametani Fuyuki , Higuchi Keiichi 
Published: February 2015

Significance
Apolipoprotein (apo) A-II is the most important protein associated with senile amyloidosis. Because some variants of apoA-II protein have been found among inbred strains of mice, we hypothesized that investigating amyloidogenesis of the variants would improve our understanding of the molecular and biological mechanisms of senile amyloidosis. Here, we demonstrate that mice with type F apoA-II (APOA2F) protein were absolutely resistant to senile amyloidosis. Moreover, a selective C-terminal APOA2F peptide inhibited fibril formation of amyloidogenic apoA-II in vitro and prevented senile amyloidosis in mice. We propose an inhibitory model in which the C-terminal APOA2F peptide prevents further fibril extension by blocking the active ends of seeds. This approach could provide a novel therapeutic option for the treatment of senile amyloidosis.
Warning signals for eruptive events in spreading fires
Authors: Fox Jerome M. , Whitesides George M. 
Published: February 2015

Significance
As flames spread through forests, buildings, or other complex environments, they can erupt, unexpectedly, into fast-moving conflagrations. This study presents evidence that characteristic patterns in the behavior of spreading flames may indicate when such eruptions are likely to occur. Our results rely on the detection of a phenomenon termed “critical slowing down”—the slowed recovery of multistable systems from perturbations as those systems approach tipping points. Using a bistable combustion system in which flames propagate either as small, slowly moving flames, or as large, rapidly moving flames stabilized by feedback between wind and fire, we provide evidence that slowing responses of spreading flames to sudden changes in environment (e.g., wind, terrain) may anticipate the onset of intense, feedback-stabilized modes of propagation.
Visualizing monolayers with a water-soluble fluorophore to quantify adsorption, desorption, and the double layer
Authors: Shieh Ian C. , Zasadzinski Joseph A. 
Published: February 2015

Significance
Visualizing phase separation in monolayers at the air–water interface with fluorescence microscopy has, up to now, relied on image contrast provided by fluorescently tagged lipids. However, the tagged lipids are insoluble and cannot leave the interface, ultimately reaching high concentrations as the phase distribution changes. This can lead to alterations in phase behavior, domain shape, and fluorescence quenching. Here we show that a water-soluble dye in the subphase preferentially adsorbs into less-ordered monolayer domains and can provide quantifiable contrast in confocal microscopy images. The dye distribution in the double layer adjacent to charged monolayers can also be imaged quantitatively and used to rapidly assess the surface potential and the fractional dissociation of the monolayer lipids.
Widespread pollution of the South American atmosphere predates the industrial revolution by 240 y
Authors: Uglietti Chiara , Gabrielli Paolo , Cooke Colin A. , Vallelonga Paul , Thompson Lonnie G. 
Published: February 2015

SignificanceAn exceptionally detailed ice core from the high-altitude location of Quelccaya (Peru) contains compelling evidence that the well-known metallurgic activities performed during the Inca Empire (A.D. 1438−1532) had a negligible impact on the South American atmosphere. In contrast, atmospheric emissions of a variety of toxic trace elements in South America started to have a widespread environmental impact around A.D. 1540, ∼240 y before the industrial revolution when colonial metallurgy began to pollute the Andean atmosphere. 20th century atmospheric pollution levels were the highest on record and remain unprecedented over the entirety of human history.
Neuroinflammation triggered by β-glucan/dectin-1 signaling enables CNS axon regeneration
Authors: Baldwin Katherine T. , Carbajal Kevin S. , Segal Benjamin M. , Giger Roman J. 
Published: February 2015

SignificanceDamage to neuronal networks in the central nervous system typically results in permanent functional deficits; however, the regenerative capacity of injured neurons can be dramatically augmented by local innate immune responses. Here we investigated the molecular and cellular events that participate in immune-mediated repair of severed optic nerve axons in the mouse. We show that intraocular administration of particulate β-glucan engages the immune receptor dectin-1 expressed on retina-resident microglia and infiltrating leukocytes, to trigger enhanced axonal regeneration. Delayed administration of β-glucan by two days is as effective as administration at the time of injury, suggesting a large therapeutic window. These data elucidate a new pathway of immune-mediated neural repair that may be targeted to reverse neurological disability.
De novo production of the plant-derived alkaloid strictosidine in yeast
Authors: Brown Stephanie , Clastre Marc , Courdavault Vincent , O’Connor Sarah E. 
Published: February 2015

Significance
Plants make a wide variety of complex molecules with potent biological activities including several anticancer therapeutics. Unfortunately, plants often produce these molecules in low amounts, making them expensive to obtain. Engineering simpler organisms, such as yeast, to produce these plant-derived compounds provides one solution to production challenges. One group of plant-derived molecules, the monoterpene indole alkaloids, is synthesized from a common intermediate, strictosidine. Here, we report how we developed a yeast strain that produces strictosidine. This required introducing 21 new genes and three gene deletions into the yeast genome. This yeast strain provides an important resource for the production of expensive, complex molecules that plants normally produce in small amounts.
SLO3 auxiliary subunit LRRC52 controls gating of sperm KSPER currents and is critical for normal fertility
Authors: Zeng Xu-Hui , Yang Chengtao , Xia Xiao-Ming , Liu Min , Lingle Christopher J. 
Published: February 2015

SignificanceMammalian sperm fertility depends on coordinated activation of two sperm-specific ion channels, the alkalization-activated Ca2+-permeable sperm channel and a sperm pH-regulated K+current (KSPER) channel; both are required for fertility. In the mouse, the KSPER channel is thought to involve a complex of a pore-forming ion channel protein and subunit encoded by theslo3gene subunit and the leucine-rich-repeat-containing protein 52 (LRRC52) auxiliary subunit. We now show that KO of LRRC52 results in severely compromised fertility and shifts KSPER current activation away from the physiological range. Furthermore, utilizing genotypes with differing average amounts of KSPER current, we show that sperm fertility exhibits a steep dependence on the amount of available KSPER current. The results establish that LRRC52 is a critical determinant of sperm KSPER function and essential to support normal fertility.
Glucose-responsive insulin activity by covalent modification with aliphatic phenylboronic acid conjugates
Authors: Chou Danny Hung-Chieh , Webber Matthew J. , Tang Benjamin C. , Lin Amy B. , Thapa Lavanya S. , Deng David , Truong Jonathan V. , Cortinas Abel B. , Langer Robert , Anderson Daniel G. 
Published: February 2015

Significance
Self-administered insulin is the most important therapeutic to provide control over blood glucose levels for patients with type-1 diabetes. However, standard insulin therapy introduces a number of complications and subsequent issues with control of blood glucose levels. Here, we prepared a derivative of insulin with a molecular switch to provide glucose-mediated activation of the insulin molecule, toward the generation of more autonomous therapy with improved blood glucose control. This modified insulin, when administered in a diabetic mouse model, restores blood glucose levels following a glucose challenge (i.e., a simulated meal) faster than both standard insulin and a clinically used long-lasting insulin derivative.
Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer
Authors: Mintz Paul J. , Rietz Anna Cecilia , Cardó-Vila Marina , Ozawa Michael G. , Dondossola Eleonora , Do Kim-Anh , Kim Jeri , Troncoso Patricia , Logothetis Christopher J. , Sidman Richard L. , Pasqualini Renata , Arap Wadih 
Published: February 2015

Significance
For the management of prostate cancer it has remained a significant clinical challenge to identify biomarkers that can be used as prognostic indicators to facilitate early treatment decisions and indicate patients at risk for castrate-resistant bone-metastatic prostate cancer in need of more aggressive treatment. In this report, serum antibodies to alpha-2–Heremans–Schmidt glycoprotein (fetuin-A) were demonstrated to display increased reactivity with concomitant development of metastatic castrate-resistant disease in a large cohort of prostate cancer patients. Furthermore, metastatic prostate cancer cell lines and bone metastasis samples displayed robust fetuin-A expression. To our knowledge, this is the first report to indicate that serum autoantibodies reactive to fetuin-A show utility as a prognostic indicator for prostate cancer patients at risk for progressing to metastatic disease.