bluuebunny/crossref_metadata_2025_split huggingface dataset:
L-selectin shedding is activated specifically within transmigrating pseudopods of monocytes to regulate cell polarity in vitro
Authors: Rzeniewicz Karolina , Newe Abigail , Rey Gallardo Angela , Davies Jessica , Holt Mark R. , Patel Ashish , Charras Guillaume T. , Stramer Brian , Molenaar Chris , Tedder Thomas F. , Parsons Maddy , Ivetic Aleksandar 
Published: March 2015

SignificanceDuring an inflammatory response, L-selectin, an immune cell-specific adhesion molecule, guides monocytes from the bloodstream toward the surrounding extravascular environment (termed “transmigration”). We show, under conditions that mimic blood flow, that L-selectin is proteolytically cleaved (or shed) exclusively within leading migratory fronts (pseudopods) of actively transmigrating monocytes. Calmodulin/L-selectin interaction, which acts to block shedding, is lost through Ser phosphorylation of the L-selectin cytoplasmic tail, occurring specifically within transmigrating pseudopods. Blocking L-selectin shedding specifically during transmigration increases pseudopod numbers, leading to defective front/back polarity that is essential for migration. These findings are the first to report, to our knowledge, an extended role for L-selectin in regulating morphological changes in leukocytes that are required for migration.
Methane transport from the active layer to lakes in the Arctic using Toolik Lake, Alaska, as a case study
Authors: Paytan Adina , Lecher Alanna L. , Dimova Natasha , Sparrow Katy J. , Kodovska Fenix Garcia-Tigreros , Murray Joseph , Tulaczyk Slawomir , Kessler John D. 
Published: March 2015

Significance
Methane, a greenhouse gas, contributes to global warming. We show that methane-rich water from the seasonally thawed active layer in the Arctic flows into Toolik Lake, Alaska. This may be an important previously unrecognized conduit for methane transport and emissions in Arctic lakes. The controls on methane input from the active layer are fundamentally different than those affecting methane production within lakes, and the response of these processes to climate and environmental change is also distinct. The accuracy of predictions of methane emissions and ultimately the extent of climate change that can be expected in the Arctic depend on a better understanding of methane dynamics in the region, including the controls over methane production and transport processes within the active layer.
Regulation of Nrf2 signaling and longevity in naturally long-lived rodents
Authors: Lewis Kaitlyn N. , Wason Emily , Edrey Yael H. , Kristan Deborah M. , Nevo Eviatar , Buffenstein Rochelle 
Published: March 2015

Significance
Both genetically altered and naturally long-lived mammals are more resistant to toxic compounds that may cause cancer and age-associated diseases than their shorter-lived counterparts. The mechanisms by which this stress resistance occurs remain elusive. We found that longer-lived rodent species had markedly higher levels of signaling activity of the multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) and that this increase in cytoprotective signaling appeared to be due to species differences in Kelch-like ECH-Associated Protein 1 (Keap1) and β-transducin repeat-containing protein (βTrCP) regulation of Nrf2 activity. Both of these negative regulators of Nrf2-signaling activity are significantly lower in longer-lived species. By targeting the proteins that regulate Nrf2 rather than Nrf2 itself, we may be able to identify new therapies that impact aging and age-associated diseases such as cancer.
Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea
Authors: Son Eun Jin , Ma Ji-Hyun , Ankamreddy Harinarayana , Shin Jeong-Oh , Choi Jae Young , Wu Doris K. , Bok Jinwoong 
Published: March 2015

Significance
Sound frequency discrimination is crucial for daily activities throughout the animal kingdom. This process begins at the auditory peripheral organ known as the organ of Corti in mammals and basilar papilla in birds. This frequency tuning is facilitated by specific anatomical and physiological properties, including gradual changes in the shape of the mechanosensory hair cells and the total number of stereocilia per hair cell along the cochlea. Unlike in birds, the molecular mechanism(s) that establishes this tonotopic organization is not known in mammals. In this study, we provide in vivo evidence that Sonic Hedgehog signaling mediates regional identity of the developing cochlea in both mammals and birds, and this regional identity prefigures the tonotopic organization in the basilar papilla.
Endocytic proteins drive vesicle growth via instability in high membrane tension environment
Authors: Walani Nikhil , Torres Jennifer , Agrawal Ashutosh 
Published: March 2015

Significance
Biological cells are engaged in an incessant uptake of macromolecules for nutrition and inter- and intracellular communication; this entails significant local bending of the plasma membrane and formation of cargo-carrying vesicles executed by a designated set of membrane-deforming proteins. The energetic cost incurred in forming vesicles is directly related to the stressed state of the membrane and, hence, that of the cell. In this study, we reveal a protein-induced “snap-through instability” that offsets tension and drives vesicle growth during clathrin-mediated endocytosis, the main pathway for the transport of macromolecules into cells. Because these proteins (actin and BAR proteins) are involved in other interfacial rearrangements in cells, the predicted instability could be at play in cells at-large.
A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling
Authors: Bai Zhiyong , Grant Barth D. 
Published: March 2015

Significance
Endosomes are membrane-bound organelles that are required for the sorting of membrane-associated proteins and lipids. Once integral membrane proteins reach the endosomal system they can be sent to the lysosome for degradation, recycled to the plasma membrane, or recycled to the Golgi apparatus. Here we provide insight into the molecules that mediate a poorly understood route to the Golgi from recycling endosomes. The mediators of this transport step that we identified include the membrane-binding and -bending TOCA proteins, the small GTPase CDC-42, associated polarity proteins PAR-6 and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex. Many transmembrane proteins likely use this same transport mechanism.
Origins of narcissism in children
Authors: Brummelman Eddie , Thomaes Sander , Nelemans Stefanie A. , Orobio de Castro Bram , Overbeek Geertjan , Bushman Brad J. 
Published: March 2015

Significance
Narcissistic individuals feel superior to others, fantasize about personal successes, and believe they deserve special treatment. When they feel humiliated, they often lash out aggressively or even violently. Unfortunately, little is known about the origins of narcissism. Such knowledge is important for designing interventions to curtail narcissistic development. We demonstrate that narcissism in children is cultivated by parental overvaluation: parents believing their child to be more special and more entitled than others. In contrast, high self-esteem in children is cultivated by parental warmth: parents expressing affection and appreciation toward their child. These findings show that narcissism is partly rooted in early socialization experiences, and suggest that parent-training interventions can help curtail narcissistic development and reduce its costs for society.
Equality bias impairs collective decision-making across cultures
Authors: Mahmoodi Ali , Bang Dan , Olsen Karsten , Zhao Yuanyuan Aimee , Shi Zhenhao , Broberg Kristina , Safavi Shervin , Han Shihui , Nili Ahmadabadi Majid , Frith Chris D. , Roepstorff Andreas , Rees Geraint , Bahrami Bahador 
Published: March 2015

Significance
When making decisions together, we tend to give everyone an equal chance to voice their opinion. To make the best decisions, however, each opinion must be scaled according to its reliability. Using behavioral experiments and computational modelling, we tested (in Denmark, Iran, and China) the extent to which people follow this latter, normative strategy. We found that people show a strong equality bias: they weight each other’s opinion equally regardless of differences in their reliability, even when this strategy was at odds with explicit feedback or monetary incentives.
Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish
Authors: Ma Yunyong , Juntti Scott A. , Hu Caroline K. , Huguenard John R. , Fernald Russell D. 
Published: March 2015

Significance
The hypothalamus controls reproductive development and function via a small peptide, gonadotropin releasing hormone (GnRH1), delivered to the pituitary. To be effective, GnRH1 must be released in a pulsatile manner, but it is not known how this is achieved. We recorded from pairs of genetically labeled GnRH1 neurons in the brains of reproductively active fish and show that these cells are strongly and uniformly interconnected by electrical synapses that can be reversibly blocked. These electrical synapses likely contribute to the pulsatile firing of GnRH1 neurons, producing the coordinated output needed for reproduction, the most important act of any organism.
Environmental stress induces trinucleotide repeat mutagenesis in human cells
Authors: Chatterjee Nimrat , Lin Yunfu , Santillan Beatriz A. , Yotnda Patricia , Wilson John H. 
Published: March 2015

SignificanceEnvironmental stress induces complex cellular responses that improve the odds of survival. One effect of the cellular stress response is to relax the fidelity of DNA repair, with the counterintuitive strategy of increasing mutagenesis to improve fitness. Because microsatellite repeats, which are intrinsically highly mutable, serve as tuning knobs for evolutionary change, we asked whether environmental stress increased their mutagenesis. We found that cold, heat, hypoxic, and oxidative stresses induce trinucleotide repeat (TNR) mutagenesis, in a way that depends on stress response factors and apparently involves DNA rereplication. Because TNRs are overrepresented in gene-regulatory proteins, stress-induced TNR mutagenesis may provide a path for the environment to subtly alter gene regulatory networks—with attendant changes in cell behavior—during development, disease, and evolution.
Latent structure in random sequences drives neural learning toward a rational bias
Authors: Sun Yanlong , O’Reilly Randall C. , Bhattacharyya Rajan , Smith Jack W. , Liu Xun , Wang Hongbin 
Published: March 2015

SignificanceThe human mind has a unique capacity to find order in chaos. The way the neocortex integrates information over time enables the mind to capture rich statistical structures embedded in random sequences. We show that a biologically motivated neural network model reacts to not only how often a pattern occurs (mean time) but also when a pattern is first encountered (waiting time). This behavior naturally produces the alternation bias in the gambler’s fallacy and provides a neural grounding for the Bayesian models of human behavior in randomness judgments. Our findings support a rational account for human probabilistic reasoning and a unifying perspective that connects the implicit learning without instruction with the generalization under structured and expressive rules.
ORMDL orosomucoid-like proteins are degraded by free-cholesterol-loading–induced autophagy
Authors: Wang Shuhui , Robinet Peggy , Smith Jonathan D. , Gulshan Kailash 
Published: March 2015

Significance
Accumulation of toxic lipids in macrophages or human plaques leads to endoplasmic reticulum (ER) stress and induction of autophagy. However, the mechanism by which ER stress and autophagy help in fine tuning cellular lipid homeostasis to counter free-cholesterol toxicity is not clear. Our studies demonstrate that cholesterol induces the translocation of ORMDL orosomucoid-like proteins out of the ER and targets them to autophagosomes, thereby relieving their negative regulation on cellular de novo sphingolipid synthesis. In addition, ORMDL3 has been recently implicated in childhood asthma and in eosinophil trafficking and activation. Thus, our finding of increased turnover of ORMDL proteins by free cholesterol is relevant not only in context to atherosclerotic disease progression but may also shed new insights on lipid homeostasis in other human diseases.
Visual Turing test for computer vision systems
Authors: Geman Donald , Geman Stuart , Hallonquist Neil , Younes Laurent 
Published: March 2015

Significance
In computer vision, as in other fields of artificial intelligence, the methods of evaluation largely define the scientific effort. Most current evaluations measure detection accuracy, emphasizing the classification of regions according to objects from a predefined library. But detection is not the same as understanding. We present here a different evaluation system, in which a query engine prepares a written test (“visual Turing test”) that uses binary questions to probe a system’s ability to identify attributes and relationships in addition to recognizing objects.
Environments and trypanosomiasis risks for early herders in the later Holocene of the Lake Victoria basin, Kenya
Authors: Chritz Kendra L. , Marshall Fiona B. , Zagal M. Esperanza , Kirera Francis , Cerling Thure E. 
Published: March 2015

Significance
Herding was the earliest form of African food production and transformed local populations of people and animals. Herders migrated from eastern to southern Africa around 2,000 years ago, but only in small numbers. Zoonotic disease vectors, specifically the tsetse fly, which carries sleeping sickness, are thought to have impeded these movements. Archaeologists have argued that the presence of tsetse flies around Lake Victoria, Kenya, created a barrier that prevented migration and forced subsistence diversification. This study, using stable isotope analysis of animal teeth, reveals the existence of ancient grassy environments east of Lake Victoria, rather than tsetse-rich bushy environments. This overturns previous assumptions about environmental constraints on livestock management in a key area for southward movement of early herders.
Propensity of undulatory swimmers, such as worms, to go against the flow
Authors: Yuan Jinzhou , Raizen David M. , Bau Haim H. 
Published: March 2015

Significance
Undulating swimmers, such as worms, are ubiquitous and play important roles in the ecosystem; agriculture; human, animal, and plant health; and medical research. The ability of undulatory swimmers to align against the flow (rheotax) is important in the animals’ life cycles, enabling them to navigate their environment and to maintain their positions in the presence of adverse flows such as in the hosts’ guts and blood vessels. We elucidate, for the first time to our knowledge, the mechanism responsible for rheotaxis in low-Reynolds-number, undulatory swimmers. This knowledge will provide a better understanding of the animals’ life cycles, will enable the development of strategies to disturb their life cycles, and will improve the design of microfluidic devices for biological research.
Synchronous down-modulation of miR-17 family members is an early causative event in the retinal angiogenic switch
Authors: Nunes Diana N. , Dias-Neto Emmanuel , Cardó-Vila Marina , Edwards Julianna K. , Dobroff Andrey S. , Giordano Ricardo J. , Mandelin Jami , Brentani Helena P. , Hasselgren Catrin , Yao Virginia J. , Marchiò Serena , Pereira Carlos A. B. , Passetti Fabio , Calin George A. , Sidman Richard L. , Arap Wadih , Pasqualini Renata 
Published: March 2015

Significance
Retinal angiogenesis is a finely tuned biological phenomenon and a major cause of blindness. We studied the regulation of this phenomenon and identified cross-talk involving microRNAs (miRs) that share the same seed sequence, transcription factors, and angiogenesis effectors. In a mouse model of retinopathy of prematurity, we show the down-regulation of all miR-17 family members as an early event in the angiogenic switch, which resulted in increased levels of hypoxia-inducible factor-1α and Vegfa in vitro. Notably, this coordinated regulation did not require the marked quantitative alterations of an individual miR but instead, relied on synchronous changes in members that share the same seed sequence. These results identify potential therapeutic targets in eye diseases with abnormal retinal angiogenesis.
Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors
Authors: Bye Chris R. , Jönsson Marie E. , Björklund Anders , Parish Clare L. , Thompson Lachlan H. 
Published: March 2015

Significance
An important challenge for improving cell-based approaches for Parkinson’s disease is the development of techniques that facilitate greater standardization of the donor material. This report describes the enrichment of transplantable progenitors for dopamine neurons from the ventral mesencephalon based on targeting of transmembrane proteins. It is an important step toward the development of clinically relevant techniques that allow for greater standardization of cell preparations used in transplantation and potentially, more predictable clinical outcomes. The findings are highly relevant for current efforts to develop stem cell-based therapies for Parkinson’s disease, where current techniques yield mixed cell populations that may contain unwanted cell types and thus, would benefit from a cell selection step prior to grafting.
Orbital forcing of climate 1.4 billion years ago
Authors: Zhang Shuichang , Wang Xiaomei , Hammarlund Emma U. , Wang Huajian , Costa M. Mafalda , Bjerrum Christian J. , Connelly James N. , Zhang Baomin , Bian Lizeng , Canfield Donald E. 
Published: March 2015

SignificanceThere is a wealth of evidence pointing to dramatic short-term climate change on Earth over the last few million years. Much of this climate change is driven by variations of Earth’s orbit around the Sun with characteristic frequencies known as Milankovitch cycles. Robust evidence for orbitally driven climate change, however, becomes rare as one descends deep into Earth time. We studied an exceptional record of climate change as recorded in 1.4-billion-year-old marine sediments from North China. This record documents regular changes in subtropical/tropical Hadley Cell dynamics. These changes in dynamics controlled wind strength, rainfall, and ocean circulation, translated into cyclic variations in sediment geochemistry, much like the orbital control on climate today and in the recent past.
Arabidopsis
DET1 degrades HFR1 but stabilizes PIF1 to precisely regulate seed germination
Authors: Shi Hui , Wang Xin , Mo Xiaorong , Tang Chao , Zhong Shangwei , Deng Xing Wang 
Published: March 2015

Significance
How organisms respond to environment changes is a fundamental and intriguing question in biology. Light is the energy resource and a crucial environmental cue for plant major developmental switches, such as seed germination. Studying the underlying mechanism is important for us to understand the basic principles of plant development and improve crop productions. Here we identify DET1 as a novel central repressor of seed germination. We further reveal that seeds use a multilevel regulatory circuit of triple feed-forward loops to sensitively and precisely mediate light-regulated germination. This study provides a comprehensive framework of how light regulates seed germination.
Thermostable ricin vaccine protects rhesus macaques against aerosolized ricin: Epitope-specific neutralizing antibodies correlate with protection
Authors: Roy Chad J. , Brey Robert N. , Mantis Nicholas J. , Mapes Kelly , Pop Iliodora V. , Pop Laurentiu M. , Ruback Stephen , Killeen Stephanie Z. , Doyle-Meyers Lara , Vinet-Oliphant Heather S. , Didier Peter J. , Vitetta Ellen S. 
Published: March 2015

Significance
Ricin toxin (RT) is a CDC-designated select agent that can be dispersed as an aerosol. In mammals, aerosolized RT causes rapid and irreversible necrosis of the lung epithelium, multifocal hemorrhagic edema, and death within 24–36 h. A safe and effective recombinant subunit vaccine (RiVax) has been developed and formulated as a thermostable, lyophilized, adjuvant-containing “powder.” This formulation of RiVax elicited neutralizing antibodies against RT, which protected macaques from the lethality of aerosolized RT. The epitope-specific antibody responses in macaques revealed a distinctive profile that was also observed in vaccinated humans. This profile might represent a signature of protection in both species.
Microbial community transcriptional networks are conserved in three domains at ocean basin scales
Authors: Aylward Frank O. , Eppley John M. , Smith Jason M. , Chavez Francisco P. , Scholin Christopher A. , DeLong Edward F. 
Published: March 2015

Significance
Microbes drive biogeochemical cycles across the globe, collectively playing a central role in shaping the biosphere. Despite their immense importance, the in situ activities of communities of microbes, in particular uncultivated lineages of “microbial dark matter,” remain poorly elucidated. In this study, we report that common temporal and ecological dynamics underpin disparate marine microbial communities, providing the first evidence that trans-Pacific diurnal transcriptional patterns in these communities may regulate ecological and biogeochemical processes across the ocean. In total, our findings indicate a remarkable regularity in the timing of community-wide activity in the ocean, and suggest that global patterns of a variety of biogeochemical transformations may be temporally predictable and governed by structured ecological determinants.
Thermal stability of cytochrome c′ from mesophilic Shewanella amazonensis
Authors: Kato Yuki , Fujii Sotaro , Kuribayashi Taka-aki , Masanari Misa , Sambongi Yoshihiro 
Published: March 2015

Abstract
Cytochrome c′ (SACP) from mesophilic Shewanella amazonensis, growing optimally at 37 °C, was thermally more stable than cytochrome c′ (AVCP) from mesophilic Allochromatium vinosum, growing optimally at 25 °C. In contrast, SACP was less stable than cytochrome c′ (PHCP) from thermophilic Hydrogenophilus thermoluteolus, growing optimally at 52 °C. Although only 28% of the SACP amino acid sequence was identical to those of AVCP and PHCP, the latter two being 55% identical, the overall main chain structures of the three cytochromes c′ were similar, and SACP exhibited thermal stability intermediate between those of AVCP and PHCP. For these three proteins, the higher the stability is, the lesser the number of Gly residues in the putative α-helical regions is. Cytochromes c′ including the present three are suitable for examining the protein stabilization mechanisms, because they are structurally similar and available from environments with a wide range of temperatures.
The time lag between a carbon dioxide emission and maximum warming increases with the size of the emission
Authors: Zickfeld Kirsten , Herrington Tyler 
Published: March 2015

Abstract
In a recent letter, Ricke and Caldeira (2014 Environ. Res. Lett.

9 124002) estimated that the timing between an emission and the maximum temperature response is a decade on average. In their analysis, they took into account uncertainties about the carbon cycle, the rate of ocean heat uptake and the climate sensitivity but did not consider one important uncertainty: the size of the emission. Using simulations with an Earth System Model we show that the time lag between a carbon dioxide (CO2) emission pulse and the maximum warming increases for larger pulses. Our results suggest that as CO2 accumulates in the atmosphere, the full warming effect of an emission may not be felt for several decades, if not centuries. Most of the warming, however, will emerge relatively quickly, implying that CO2 emission cuts will not only benefit subsequent generations but also the generation implementing those cuts.