bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conserved regulatory mechanism controls the development of cells with rooting functions in land plants
Authors: Tam Thomas Ho Yuen , Catarino Bruno , Dolan Liam 
Published: July 2015

Significance
This work describes the discovery of an ancient genetic mechanism that was used to build rooting systems when plants colonized the relatively dry continental surfaces >470 million years ago. We demonstrate that a group of basic helix–loop–helix transcription factors—the LOTUS JAPONICUS ROOTHAIRLESS1-LIKE proteins—is part of a conserved auxin-regulated gene network that controls the development of tip-growing cells with rooting functions among extant land plants. This result suggests that this mechanism was active in the common ancestor of most land plants and facilitated the development of early land plant filamentous rooting systems, crucial for the successful colonization of the land by plants.
Climatic controls on ecosystem resilience: Postfire regeneration in the Cape Floristic Region of South Africa
Authors: Wilson Adam M. , Latimer Andrew M. , Silander John A. 
Published: July 2015

SignificanceThe rate at which ecosystems recover from disturbance can greatly influence their resilience to environmental change. We used more than a decade of satellite data to model how the extraordinarily biodiverse shrublands of South Africa recover following fire and how recovery rates vary with temperature and precipitation across the region. We found that climate strongly affects how quickly plant communities can recover after fire. We also used global climate models to project ecosystem recovery into the future and found that warmer winter temperatures will likely speed up postfire recovery unless precipitation declines as temperature increases (as some models project).
Insular neural system controls decision-making in healthy and methamphetamine-treated rats
Authors: Mizoguchi Hiroyuki , Katahira Kentaro , Inutsuka Ayumu , Fukumoto Kazuya , Nakamura Akihiro , Wang Tian , Nagai Taku , Sato Jun , Sawada Makoto , Ohira Hideki , Yamanaka Akihiro , Yamada Kiyofumi 
Published: July 2015

Significance
Patients with addiction have a greater tendency to engage in risk-taking behavior. However, the neural substrates responsible for these deficits remain unknown. Here we demonstrated that chronic methamphetamine-treated rats preferred high-risk/high-reward actions and assigned higher value to high returns, indicative of altered decision-making. Pharmacological studies revealed that the insular neural system controls decision-making in both healthy and methamphetamine-treated rats. We further confirmed the role of the insular cortex in decision-making using designer receptor exclusively activated by designer drug technology. Because decision-making is a cognitive process that influences many aspects of daily living and both mental and physical health, the findings of this study have broader implications.
Twentieth century surge of excess adult male mortality
Authors: Beltrán-Sánchez Hiram , Finch Caleb E. , Crimmins Eileen M. 
Published: July 2015

Significance
Female life expectancy now exceeds that of males in all countries. Although this gender difference has become accepted as normal, it is a relatively recent demographic phenomenon that emerged with the reduction of infections and the increase in the share of adult mortality attributed to cancer and cardiovascular disease. Heart disease is the main condition associated with increased excess male mortality, making the strongest contributions in birth cohorts of 1900–1935. Smoking behavior accounts for about 30% of male excess mortality at ages 50–70 for those born in 1900–1935. The remaining excess male mortality may be explained by underlying traits of vulnerability to cardiovascular disease that emerged with the reduction of infections and changes in diet and other lifestyle factors.
Measuring selective constraint on fertility in human life histories
Authors: Jones James Holland , Tuljapurkar Shripad 
Published: July 2015

Significance
Trade-offs, or constraints, play a substantial role in shaping the ability of organisms to respond adaptively to selection. We derive a simple means for measuring constraints in demographic rates like fertility and survival that builds on commonly used evolutionary demographic measures. We apply this measure to a hypothesized trade-off between fertility and infant survival and show that a 1% reduction in infant mortality would have to be balanced by an approximately 20% increase in fertility to be favored by selection. Our paper should have an important impact on shaping future empirical studies of human life histories and parental investment as it identifies key measures that we expect should be quite variable with respect to ecology, technology, and social systems.
Inferring influenza dynamics and control in households
Authors: Lau Max S.Y. , Cowling Benjamin J. , Cook Alex R. , Riley Steven 
Published: July 2015

SignificanceTraditionally, the efficacy of household-based nonpharmaceutical interventions against influenza is measured by the household secondary attack rate based on observed individual epidemiological data. We present an alternative measure of intervention efficacy that accounts for unobserved transmission using Bayesian techniques. We apply our methods to data from a study of household interventions (face masks and improved hand hygiene) in Hong Kong. This paper describes advances in our understanding of an important disease system and also our statistical ability to synthesize modern data streams.
Biased Brownian motion as a mechanism to facilitate nanometer-scale exploration of the microtubule plus end by a kinesin-8
Authors: Shin Yongdae , Du Yaqing , Collier Scott E. , Ohi Melanie D. , Lang Matthew J. , Ohi Ryoma 
Published: July 2015

Significance
The cellular distributions of kinesins are defined in part by their intrinsic biophysical properties. The well-characterized kinesin-8s, for example, translocate exceptionally long distances on a microtubule track, concentrating them at plus ends of long, stable microtubules. Kif18B, a little-studied kinesin-8, targets the plus ends of fast-growing, short-lived microtubules by binding the plus-end tracking protein EB1. Whether ultraprocessivity is conserved among kinesin-8s is thus unclear. Here, we show that Kif18B is not ultraprocessive and that the motor switches frequently between diffusive and directed modes of motility. Our work identifies properties of Kif18B that may have optimized the motor to explore the ∼1-μm domain of microtubule plus ends and show that biophysical motor properties cannot be generalized within any one kinesin subfamily.
Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia
Authors: Lo Chun-Yi Zac , Su Tsung-Wei , Huang Chu-Chung , Hung Chia-Chun , Chen Wei-Ling , Lan Tsuo-Hung , Lin Ching-Po , Bullmore Edward T. 
Published: July 2015

Significance
Using network analysis of resting-state functional MRI data, we demonstrate that significant randomization of global network metrics, and greater resilience to targeted attack on network hubs, was replicably demonstrable in Chinese patients with schizophrenia, and was also demonstrated for the first time in their nonpsychotic first-degree relatives. These results support the hypothesis that functional networks are abnormally randomized and resilient in schizophrenia and indicate that network randomization/resilience may be an endophenotype, or marker of familial risk, for schizophrenia. We suggest that the greater randomization of the brain network endophenotype of schizophrenia may confer advantages in terms of greater resilience to pathological attack that may explain the selection and persistence of risk genes for schizophrenia in the general population.
Rapid and widespread de novo evolution of kin discrimination
Authors: Rendueles Olaya , Zee Peter C. , Dinkelacker Iris , Amherd Michaela , Wielgoss Sébastien , Velicer Gregory J. 
Published: July 2015

Significance
Relatedness-dependent behavior modification is common among social organisms and has been a major feature of social evolution theory for decades. However, the evolutionary causes of kin discrimination are often unclear. Here, we document many spontaneous origins of kin discrimination in a social microbe that appear to arise as indirect byproducts of adaptation at other traits and we show that kin discrimination evolves by diverse genetic mechanisms.
Quantification of biological aging in young adults
Authors: Belsky Daniel W. , Caspi Avshalom , Houts Renate , Cohen Harvey J. , Corcoran David L. , Danese Andrea , Harrington HonaLee , Israel Salomon , Levine Morgan E. , Schaefer Jonathan D. , Sugden Karen , Williams Ben , Yashin Anatoli I. , Poulton Richie , Moffitt Terrie E. 
Published: July 2015

Significance
The global population is aging, driving up age-related disease morbidity. Antiaging interventions are needed to reduce the burden of disease and protect population productivity. Young people are the most attractive targets for therapies to extend healthspan (because it is still possible to prevent disease in the young). However, there is skepticism about whether aging processes can be detected in young adults who do not yet have chronic diseases. Our findings indicate that aging processes can be quantified in people still young enough for prevention of age-related disease, opening a new door for antiaging therapies. The science of healthspan extension may be focused on the wrong end of the lifespan; rather than only studying old humans, geroscience should also study the young.
Structure and mechanism of the ATPase that powers viral genome packaging
Authors: Hilbert Brendan J. , Hayes Janelle A. , Stone Nicholas P. , Duffy Caroline M. , Sankaran Banumathi , Kelch Brian A. 
Published: July 2015

Significance
Many viruses use a molecular motor to pump DNA into a preformed protein shell called the capsid, a process that is essential for the formation of infectious virus particles. The ATPase machine powering this process is the strongest known biological motor. However, the structure and mechanism of this motor are unknown. Here, we derive a structural model of the ATPase assembly using a combination of X-ray crystallography, small-angle X-ray scattering, molecular modeling, and biochemical data. We identify residues critical for ATP hydrolysis and DNA binding, and derive a mechanistic model for the translocation of DNA into the viral capsid. Our studies introduce a model for ATPase assembly and illustrate how DNA is pumped with high force.
Sequential ubiquitination and deubiquitination enzymes synchronize the dual sensor and effector functions of TRIM21
Authors: Fletcher Adam J. , Mallery Donna L. , Watkinson Ruth E. , Dickson Claire F. , James Leo C. 
Published: July 2015

Significance
Tripartite motif (TRIM) proteins are a large family of E3 ubiquitin (Ub) ligases, with many members having important roles in innate immunity. TRIM21 is a cytosolic antibody receptor that recognizes the Fc portion of antibodies bound to incoming virions. On binding to these immune complexes, TRIM21 triggers the catastrophic disassembly of viral capsids at the proteasome, terminating viral infection. Simultaneously, TRIM21 “senses” the presence of the virus and provokes signaling cascades that activate the transcription factor NF-κB, ultimately alerting surrounding cells to the infection. Here, we uncover the stepwise ubiquitination mechanism catalyzed by TRIM21, as well as the various cofactors required, that allows these two antiviral activities to occur synchronously at the proteasome.
Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters
Authors: Montiel Daniel , Kang Hahk-Soo , Chang Fang-Yuan , Charlop-Powers Zachary , Brady Sean F. 
Published: July 2015

Significance
A rapidly growing number of cryptic natural product biosynthetic gene clusters have been identified in bacterial DNA sequencing datasets. The metabolites encoded by most of these gene clusters remain uncharacterized because they are not readily activated using monoculture fermentation methods. The development of generic gene cluster activation strategies is needed to access molecules encoded by this rapidly growing collection of sequenced gene clusters. The promoter engineering platform outlined here provides a simple, cost-effective, and potentially scalable tool for the characterization of molecules encoded by gene clusters found in sequenced microbial (meta)genomes. We believe that this gene cluster activation platform will accelerate the discovery of biomedically relevant metabolites using (meta)genomics-driven natural products discovery methods.
Intergenerational neural mediators of early-life anxious temperament
Authors: Fox Andrew S. , Oler Jonathan A. , Shackman Alexander J. , Shelton Steven E. , Raveendran Muthuswamy , McKay D. Reese , Converse Alexander K. , Alexander Andrew , Davidson Richard J. , Blangero John , Rogers Jeffrey , Kalin Ned H. 
Published: July 2015

Significance
According to the World Health Organization, anxiety and depressive disorders are a leading source of disability, affecting hundreds of millions of people. Children can inherit an extremely anxious temperament, which is a prominent risk factor for the later development of anxiety, depression, and comorbid substance abuse. This study uses high-resolution functional and structural imaging in our well-established developmental nonhuman primate model to identify the heritable neural substrate that underlies extreme childhood anxious temperament. Using a large multigenerational family pedigree, genetic correlation analyses revealed a tripartite neural circuit where metabolism likely shares a genetic substrate with early-life dispositional anxiety. Interestingly, we found that brain function—not structure—is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.
What the fly’s nose tells the fly’s brain
Authors: Stevens Charles F. 
Published: July 2015

Significance
This work is significant for three reasons. First, a new way the brain represents information is identified, one in which the information present in a large population of neurons can be gotten from a small subset of any neurons rather that from a subset of certain specific neurons. Second, the nature of the combinatorial code used to specify odor identity is identified, and this same type of code may be used in other contexts. Third, the way fly olfaction works can potentially provide a model for understanding the function of important vertebrate brain regions that appear to share the same neural circuit architecture.
Spectrum of power laws for curved hand movements
Authors: Huh Dongsung , Sejnowski Terrence J. 
Published: July 2015

Significance
In curved hand movements around ellipses, the speed tends to scale inversely with the curvature with a power law having an exponent of −1/3. We examined whether this well-known regularity in motor planning holds for more general shapes. Using an optimality principle, we identified a set of basis shapes, each with a single characteristic angular frequency, which subjects drew with power laws whose exponents ranged from 0 to −2/3. More general movements exhibited linear mixtures of power laws. The speed of arbitrary doodling movements with a broad spectrum of frequencies could also be predicted from the curvature with high accuracy.
EGFR inhibition evokes innate drug resistance in lung cancer cells by preventing Akt activity and thus inactivating Ets-1 function
Authors: Phuchareon Janyaporn , McCormick Frank , Eisele David W. , Tetsu Osamu 
Published: July 2015

Significance
Lung cancer is the leading cause of cancer death worldwide. About 10% harbor mutations in epidermal growth factor receptor (EGFR). Despite remarkable progress in treatment with EGFR inhibitors, only 5% of patients achieve tumor reduction >90%, even though all of those treated have EGFR mutations. Our study addressed this discrepant response by investigating the mechanism of innate drug resistance, i.e. resistance inherent in the tumor cells even before treatment begins and not acquired over its course. Because overcoming innate resistance will increase the primary response, our findings may provide an opportunity to develop new therapies to reduce the probability of emergent resistance to EGFR inhibitors.
ALDH2(E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis
Authors: Jin Shengfang , Chen Jiang , Chen Lizao , Histen Gavin , Lin Zhizhong , Gross Stefan , Hixon Jeffrey , Chen Yue , Kung Charles , Chen Yiwei , Fu Yufei , Lu Yuxuan , Lin Hui , Cai Xiujun , Yang Hua , Cairns Rob A. , Dorsch Marion , Su Shinsan M. , Biller Scott , Mak Tak W. , Cang Yong 
Published: July 2015

Significance
About 40% of East Asians and over 500 million people worldwide carry a specific polymorphism, ALDH2*2, and exhibit “Asian flush” after alcohol drinking. We generated a mouse strain with this engineered polymorphism and demonstrated its resemblance to human carriers in terms of defective alcohol metabolism. With this model, we show that murine ALDH2*2 increases ALDH2 protein turnover and promotes chemical-induced liver tumor development. Importantly, ALDH2 is unstable in ALDH2*2 human liver samples and is significantly down-regulated in human liver tumors. Data from our mouse and clinical studies suggest that ALDH2 is a liver tumor suppressor and the ALDH2*2 polymorphism is a risk factor for liver cancer.
Measuring dynamic cell–material interactions and remodeling during 3D human mesenchymal stem cell migration in hydrogels
Authors: Schultz Kelly M. , Kyburz Kyle A. , Anseth Kristi S. 
Published: July 2015

Significance
Scaffolds that serve as synthetic mimics of the extracellular matrix have applications in wound healing, tissue engineering, and stem cell expansion. When cells are cultured in these tunable matrices, little is known about local microenvironmental changes during degradation and remodeling. Methods that provide quantitative and predictable information about cell-mediated remodeling could significantly improve the biomaterial design process. We use passive microrheology, a technique that measures rheological properties from Brownian motion of embedded particles, to characterize remodeling of a cell-laden peptide-functionalized poly(ethylene glycol) hydrogel that degrades in response to cell-secreted enzymes. Results show microenvironmental changes at multiple time and size scales, and reveal an interesting degradation gradient, as mesenchymal stem cells attach, spread, and move through these synthetic extracellular matrix mimics.
How competition governs whether moderate or aggressive treatment minimizes antibiotic resistance
Authors: Colijn C. , Cohen T. 
Published: July 2015

AbstractThe growing burden of antimicrobial resistance is one of the most challenging problems facing public health today, and understanding how our approaches for using antimicrobial drugs shapes future levels of resistance is crucial. Recently there has been debate over whether an aggressive (i.e. high dose) or more moderate (i.e. lower dose) treatment of individuals will most limit the emergence and spread of resistant bacteria. Here we demonstrate how one can understand and resolve these apparently contradictory conclusions. We show that a key determinant of which treatment strategy will perform best at the individual level is the extent of effective competition between resistant and sensitive pathogens within a host. We extend our analysis to the community level, exploring the spectrum between strict inter-strain competition and strain independence. From this perspective as well, we find that the magnitude of effective competition between resistant and sensitive strains determines whether an aggressive approach or moderate approach minimizes the burden of resistance in the population.
The Effect of Horizontal Gene Transfer on the Dynamics of Antibiotic Drug Resistance in a Unicellular Population with a Dynamic Fitness Landscape, Repression and De-repression
Authors: Atsmon-Raz Yoav , Wagner Nathaniel , Tannenbaum Emanuel David 
Published: July 2015

AbstractAntibiotic drug resistance spreads through horizontal gene transfer (HGT) via bacterial conjugation in unicellular populations of bacteria. Consequently, the efficiency of antibiotics is limited and the expected “grace period” of novel antibiotics is typically quite short. One of the mechanisms that allow the accelerated adaptation of bacteria to antibiotics is bacterial conjugation. However, bacterial conjugation is regulated by several biological factors, with one of the most important ones being repression and derepression.In recent work, we have studied the effects that repression and de-repression on the mutation-selection balance of an HGT-enabled bacterial population in a static environment. Two of our main findings were that conjugation has a deleterious effect on the mean fitness of the population and that repression is expected to allow a restoration of the fitness cost due to plasmid hosting.Here, we consider the effect that conjugation-mediated HGT has on the speed of adaptation in a dynamic environment and the effect that repression will have on the dynamics of antibiotic drug resistance. We find that, the effect of repression is dynamic in its possible outcome, that a conjugators to non-conjugators phase transition exists in a dynamic landscape as we have previously found for a static landscape and we quantify the time required for a unicellular population to adapt to a new antibiotic in a periodically changing fitness landscape. Our results also confirmed that HGT accelerates adaptation for a population of prokaryotes which agrees with current knowledge, that HGT rates increase when a population is put under stress.
On the dimensionality of olfactory space
Authors: Magnasco Marcelo O. , Keller Andreas , Vosshall Leslie B. 
Published: July 2015

AbstractWe recently presented an estimate of the number of mutually discriminable olfactory stimuli at one trillion (1). Subjects were asked to sniff mixtures of molecules with increasing component overlap selected from a panel of 128 isointense structurally and perceptually diverse monomolecular odorants (2). We considered stimulus pairs discriminable when the majority of subjects could significantly discriminate them at p=0.05, a conventional statistical threshold given our sample size. From these empirical data, we estimated that human discriminative capacity exceeds one trillion olfactory stimuli. Several readers have pointed out that such extrapolations are sensitive to underlying assumptions about the chosen significance threshold (3) and the dimensionality of olfaction (4). It is important to note that any exponential function will be sensitive in this way, and the goal of our model was not to identify the exact number of discriminable olfactory stimuli, or even the exact mathematical bounds, but an estimate of the order of magnitude of human discriminatory power across a population of human subjects. This was not clearly stated in our paper, and we agree that contradictory references to a “lower limit” and an “upper bound” were confusing. The central argument in (4) is that our estimation method assumes that the dimensionality of olfactory space is large. We agree that the high-dimensional nature of olfaction is indeed an assumption, and we should have stated this explicitly in our paper (1). Even if we follow this logic of the models presented in (4), purely geometrical calculations show that our results hold if the dimensionality of olfactory representations is D≥25. The dimensionality of olfaction is a question of interest to everyone, and while we do not know for sure, all available evidence suggests that olfaction is a high-dimensional sense. The olfactory system is wired to keep information from the ~400 odorant receptors strictly separated, so it is plausible that olfaction operates at least in 400-dimensional space. This is an important topic of discussion in olfaction, and we welcome continued debate of the dimensionality of smell and how this impacts human olfactory perception.