bluuebunny/crossref_metadata_2025_split huggingface dataset:
High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates
Authors: Roger Thierry , Schneider Anina , Weier Manuela , Sweep Fred C. G. J. , Le Roy Didier , Bernhagen Jürgen , Calandra Thierry , Giannoni Eric 
Published: February 2016

Significance
During pregnancy, high circulating levels of adenosine and prostaglandins reduce the ability of fetal immune cells to mount powerful proinflammatory responses. In contrast, newborns express 10-fold higher levels of the proinflammatory immune regulator migration inhibitory factor (MIF) compared with adults. MIF sustains cell activation and cytokine production and counterregulates adenosine and prostaglandin E2-mediated immunosuppression in newborn monocytes. Yet excessive MIF expression during an established infection worsens the outcome of newborn mice. Thus, we identify a unique role for MIF in regulating neonatal innate immune responses and propose that MIF has a protective role to reduce susceptibility to infection during the neonatal period but may favor uncontrolled inflammation during sepsis, leading to adverse outcomes.
Exceptionally strong easterly wind burst stalling El Niño of 2014
Authors: Hu Shineng , Fedorov Alexey V. 
Published: February 2016

Significance
The El Niño–Southern Oscillation is the dominant mode of climate variability in the tropical Pacific, with pronounced global teleconnections. Predicting El Niño and understanding its progression still present a challenge to climate scientists. At the beginning of 2014, many in the scientific community anticipated that a strong El Niño could potentially develop by year end, but the observed warm event barely reached the El Niño threshold. Here, we analyze satellite-based data and numerical simulations to show that an intense easterly wind burst that occurred in June of 2014 was the key dynamical factor that stalled the El Niño development. We discuss our findings in the context of limited El Niño predictability and explore links between intraseasonal wind bursts and decadal climate change.
Brain shape convergence in the adaptive radiation of New World monkeys
Authors: Aristide Leandro , dos Reis Sergio Furtado , Machado Alessandra C. , Lima Inaya , Lopes Ricardo T. , Perez S. Ivan 
Published: February 2016

SignificanceThe evolutionary diversification of brain morphology is one of the most prominent features of the primate adaptive radiation and a likely determinant of primate evolutionary success. However, the ecological factors responsible for the diversification of the primate brain are largely unknown. In this work, we use a comparative approach to study brain diversification during the adaptive radiation of a major primate clade—the New World monkeys. We show that brain morphology evolved in association with the occupation of several ecological niches, and that convergence in brain morphology among clades may be associated with an evolutionary increase in the complexity of social behaviors.
Circadian misalignment increases cardiovascular disease risk factors in humans
Authors: Morris Christopher J. , Purvis Taylor E. , Hu Kun , Scheer Frank A. J. L. 
Published: February 2016

Significance
Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease, even after controlling for traditional risk factors. Shift workers frequently undergo circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles). This misalignment has been proposed to explain, in part, why shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. However, the impact of circadian misalignment per se on 24-h blood pressure and inflammatory markers is poorly understood. We show—under highly controlled laboratory conditions—that short-term circadian misalignment increases 24-h blood pressure and inflammatory markers in healthy adults. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.
Seasonality in human cognitive brain responses
Authors: Meyer Christelle , Muto Vincenzo , Jaspar Mathieu , Kussé Caroline , Lambot Erik , Chellappa Sarah L. , Degueldre Christian , Balteau Evelyne , Luxen André , Middleton Benita , Archer Simon N. , Collette Fabienne , Dijk Derk-Jan , Phillips Christophe , Maquet Pierre , Vandewalle Gilles 
Published: February 2016

Significance
Evidence for seasonality in humans is limited. Mood probably stands as the aspect of human brain function most acknowledged as being affected by season. Yet, the present study provides compelling evidence for previously unappreciated annual variations in the cerebral activity required to sustain ongoing cognitive processes in healthy volunteers. The data further show that this annual rhythmicity is cognitive-process-specific (i.e., the phase of the rhythm changes between cognitive tasks), speaking for a complex impact of season on human brain function. Annual variations in cognitive brain function may contribute to explain intraindividual cognitive changes that could emerge at specific times of year.
Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model
Authors: Eggo Rosalind M. , Scott James G. , Galvani Alison P. , Meyers Lauren Ancel 
Published: February 2016

Significance
Asthma exacerbations are frequently triggered by common cold infections. Whereas prior studies have swabbed individual patients to detect viruses, we take a population level approach to investigate common cold circulation and its consequences for asthmatics. We introduce a dynamic model of common cold transmission with different contact patterns for adults and children, which are modified by school vacations. By jointly fitting this and an asthma risk model to daily hospitalization rates in eight large cities in Texas, we found that the common cold is a primary driver of asthma exacerbations, and both are predictably influenced by the school calendar. This provides actionable insight for assessing asthma hospitalization risk and targeting preventive measures.
Vasopressin increases human risky cooperative behavior
Authors: Brunnlieb Claudia , Nave Gideon , Camerer Colin F. , Schosser Stephan , Vogt Bodo , Münte Thomas F. , Heldmann Marcus 
Published: February 2016

Significance
Most forms of cooperative behavior take place in a mutually beneficial context where cooperation is risky as its success depends on unknown actions of others. In two pharmacological experiments, we show that intranasal administration of arginine vasopressin (AVP), a hormone that regulates mammalian social behaviors such as monogamy and aggression, increases humans’ tendency to engage in mutually beneficial cooperation. Several control tasks ruled out that AVP’s effects were driven by increased willingness to bare risks in the absence of social context, beliefs about the actions of one’s partner, or altruistic concerns. Our findings provide novel causal evidence for a biological factor underlying cooperation and are in accord with previous findings that cooperation is intrinsically rewarding for humans.
Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites
Authors: Zhang Jiantao , Zhang Zhenlu , Chukkapalli Vineela , Nchoutmboube Jules A. , Li Jianhui , Randall Glenn , Belov George A. , Wang Xiaofeng 
Published: February 2016

Significance
Positive-strand RNA viruses [(+)RNA viruses] include many important human, animal, and plant pathogens. A highly conserved and indispensable feature of (+)RNA virus infection is that these viruses proliferate and reorganize host membranes to assemble viral replication complexes (VRCs). We show that brome mosaic virus (BMV) stimulates phosphatidylcholine (PC) synthesis at the viral replication sites. BMV recruits a host enzyme involved in PC synthesis to support proper VRC formation and genomic replication. We further show that hepatitis C virus and poliovirus also promote accumulation of PC at the viral replication sites, revealing a feature common to a group of (+)RNA viruses. This virus-specific step can be targeted to develop a broad-spectrum antiviral strategy with the least side effects on host growth.
Microstructure provides insights into evolutionary design and resilience of
Coscinodiscus
sp. frustule
Authors: Aitken Zachary H. , Luo Shi , Reynolds Stephanie N. , Thaulow Christian , Greer Julia R. 
Published: February 2016

Significance
Diatoms are unicellular algae that form an intricate silica cell wall. A protective shell that is light enough to prevent sinking while simultaneously offering strength against predators is of interest to the design of lightweight structural materials. Using three-point bending experiments, we show that the diatom shell has the highest specific strength of all previously reported biological materials. Fracture analysis and finite element simulations also suggest functional differentiation between the shell layers and features to mitigate fracture. These results demonstrate the natural development of architecture in live organisms to simultaneously achieve light weight, strength, and structural integrity and may provide insight into evolutionary design.
Pliocene reversal of late Neogene aridification
Authors: Sniderman J. M. Kale , Woodhead Jon D. , Hellstrom John , Jordan Gregory J. , Drysdale Russell N. , Tyler Jonathan J. , Porch Nicholas 
Published: February 2016

Significance
The warm climates of the Pliocene epoch are considered our best analog for a future anthropogenic greenhouse world. However, understanding of the nature of Pliocene climate variability and change on land is currently limited by the poor age control of most existing terrestrial climate archives. We present a radiometrically dated history of the evolution of Southern Hemisphere vegetation and hydroclimate from the latest Miocene to the middle Pliocene. These data reveal a sharp increase in precipitation in the Early Pliocene, which drove complete vegetation turnover. The development of warm, wet early Pliocene climates clearly reversed a long-term Southern Hemisphere trend of late Neogene cooling and aridification, highlighting the question of what initiated this sustained, ∼1.5-My-long interval of warmth.
Endocytosis separates EGF receptors from endogenous fluorescently labeled HRas and diminishes receptor signaling to MAP kinases in endosomes
Authors: Pinilla-Macua Itziar , Watkins Simon C. , Sorkin Alexander 
Published: February 2016

Significance
How endocytosis regulates intracellular signaling is a major unsolved question. In this study, we labeled Ras, which plays a central role in normal and oncogenic signaling, with the fluorescent protein by gene editing, and for the first time (to our knowledge) examined the localization of endogenous Ras in living cells stimulated with epidermal growth factor (EGF). Microscopy imaging of living cells demonstrated that, although activated EGF receptors are rapidly internalized into endosomes, Ras is not present in these endosomes and mainly located in the plasma membrane. Therefore, EGF receptors signal to MAP kinases through Ras exclusively from the plasma membrane.
Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes
Authors: Maher Geoffrey J. , McGowan Simon J. , Giannoulatou Eleni , Verrill Clare , Goriely Anne , Wilkie Andrew O. M. 
Published: February 2016

Significance
A major goal in genetics is to understand the processes that shape the frequency of new mutations, particularly those causing human disease. Here, we focus on specific mutations in the male germline that, although initially rare, confer a growth or survival advantage to the stem cell, leading to clonal expansion over time: a process similar to early tumor growth and currently described only in humans. Previous studies supporting this “selfish” selection quantified mutations in sperm or testis pieces using methods that destroyed their cellular origins. Here, we pinpoint and identify pathogenic mutations directly within individual seminiferous tubules, the structures that generate spermatozoa. This methodology provides unprecedented precision in documenting the spectrum and prevalence of selfish mutations in men’s testes.
Sleep deprivation and false confessions
Authors: Frenda Steven J. , Berkowitz Shari R. , Loftus Elizabeth F. , Fenn Kimberly M. 
Published: February 2016

Significance
False confessions occur surprisingly frequently in the context of interrogations and criminal investigations. Indeed, false confessions are thought to account for approximately 15–25% of wrongful convictions in the United States. Here we demonstrate that sleep deprivation increases the likelihood that a person will falsely confess to wrongdoing that never occurred. Furthermore, our data suggest that it may be possible to identify certain individuals who are especially likely to falsely confess while sleep deprived. The present research is a crucial step toward understanding the role of sleep deprivation in the problem of false confession and, in turn, raises complex questions about the use of sleep deprivation in the interrogation of innocent and guilty suspects.
Slow dissolving of emotional distress contributes to hyperarousal
Authors: Wassing Rick , Benjamins Jeroen S. , Dekker Kim , Moens Sarah , Spiegelhalder Kai , Feige Bernd , Riemann Dieter , van der Sluis Sophie , Van Der Werf Ysbrand D. , Talamini Lucia M. , Walker Matthew P. , Schalkwijk Frans , Van Someren Eus J. W. 
Published: February 2016

Significance
Decades of research into the cause of chronic insomnia have identified hyperarousal as the key factor, but mechanisms underlying hyperarousal have remained elusive. The present findings suggest that hyperarousal can result from an inadequate resolution of emotional distress, which, in turn, is likely due to restless rapid-eye-movement sleep.
Clonally expanded CD4
+
T cells can produce infectious HIV-1 in vivo
Authors: Simonetti Francesco R. , Sobolewski Michele D. , Fyne Elizabeth , Shao Wei , Spindler Jonathan , Hattori Junko , Anderson Elizabeth M. , Watters Sarah A. , Hill Shawn , Wu Xiaolin , Wells David , Su Li , Luke Brian T. , Halvas Elias K. , Besson Guillaume , Penrose Kerri J. , Yang Zhiming , Kwan Richard W. , Van Waes Carter , Uldrick Thomas , Citrin Deborah E. , Kovacs Joseph , Polis Michael A. , Rehm Catherine A. , Gorelick Robert , Piatak Michael , Keele Brandon F. , Kearney Mary F. , Coffin John M. , Hughes Stephen H. , Mellors John W. , Maldarelli Frank 
Published: February 2016

Significance
Reservoirs of HIV-infected cells persist during antiretroviral therapy, and understanding persistence is essential to develop HIV curative strategies. During replication, HIV integrates into the host genome; most proviruses are not infectious, but some with replication-competent HIV persist. Cells with integrated HIV can proliferate, potentially expanding the reservoir, but whether cells with replication-competent HIV actually undergo expansion is unknown. HIV reactivation is often lethal to infected cells, and others have reported finding no replication-competent HIV in expanded populations. We describe a highly expanded clone containing infectious HIV that was the source of viremia for years in a patient. Clonally expanded populations can represent a long-lived reservoir of HIV. Curative strategies will require targeting this persistence mechanism.
Variable priming of a docked synaptic vesicle
Authors: Jung Jae Hoon , Szule Joseph A. , Marshall Robert M. , McMahan Uel J. 
Published: February 2016

Significance
After synaptic vesicles dock at an active zone on the presynaptic plasma membrane of axon terminals, the vesicles become primed for fusion with the membrane, an essential step in synaptic impulse transmission. We used electron tomography to examine nanometer-scale variations in structural relationships of docked vesicles at the simply arranged active zones of frog neuromuscular junctions. The results, together with prior biochemical and electrophysiological concepts, lead to the hypothesis that priming is regulated by variation in force generated by the shortening and lengthening of macromolecules in the common active zone organelle “active zone material” that links docked vesicles to presynaptic membrane components. Knowledge of mechanisms that regulate synaptic transmission is required for understanding how different synapses accomplish their specialized tasks.
A critical role for alternative polyadenylation factor CPSF6 in targeting HIV-1 integration to transcriptionally active chromatin
Authors: Sowd Gregory A. , Serrao Erik , Wang Hao , Wang Weifeng , Fadel Hind J. , Poeschla Eric M. , Engelman Alan N. 
Published: February 2016

Significance
HIV-1 requires integration for efficient gene expression, and the local chromatin environment significantly influences the level of HIV-1 transcription. Silent, integrated proviruses constitute the latent HIV reservoir. As HIV-1 commandeers cellular factors to dictate its preferred integration sites, these interactions consequentially influence latency. We examined the impact of polyadenylation specificity factor CPSF6, which binds HIV-1 capsid, and the integrase-binding chromatin reader LEDGF/p75 on viral infection and integration site distribution. Integration sites were determined in cells knocked down or knocked out for one or both host factors. Our data indicate that CPSF6 directs HIV-1 to transcriptionally active chromatin, where LEDGF/p75 predominantly directs the positions of integration within genes. These findings clarify the roles of cellular forces that dictate HIV-1 integration preferences and hence virus pathogenesis.
Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting
Authors: Ma Xuanyi , Qu Xin , Zhu Wei , Li Yi-Shuan , Yuan Suli , Zhang Hong , Liu Justin , Wang Pengrui , Lai Cheuk Sun Edwin , Zanella Fabian , Feng Gen-Sheng , Sheikh Farah , Chien Shu , Chen Shaochen 
Published: February 2016

Significance
The great challenge to developing an in vitro liver model lies in the limitation of current approaches to recapitulate the sophisticated liver microenvironment contributed by the complex microarchitecture and diverse cell combination. We demonstrate an innovative advancement toward simulating natural complexity by integrating a rapid 3D bioprinting technology with tissue engineering to develop a microscale hepatic construct consisting of physiologically relevant hexagonal units of liver cells and supporting cells. The entire construct is fabricated within several seconds on minimal UV illumination. The model enables the structural and functional improvements of human induced pluripotent stem cell-derived hepatic progenitor cells and therefore can be used in early personalized drug screening and liver pathophysiology studies in vitro.
Translation quality control is critical for bacterial responses to amino acid stress
Authors: Bullwinkle Tammy J. , Ibba Michael 
Published: February 2016

Significance
Recent studies showing that both high-accuracy protein synthesis and low-accuracy protein synthesis are critical for cellular growth and survival under different growth conditions suggest that the translation quality-control machinery may function in cellular processes other than protein synthesis. We explored this possibility and found that inhibition of misacylated-tRNA quality control suppressed the synthesis of the starvation-inducible second messenger guanosine tetraphosphate and limited the induction of stringent response-dependent gene expression. These findings show that translation quality control is a single checkpoint for both accurate protein synthesis and transcriptional responses to stress.
Ribosome Protein L4 is essential for Epstein–Barr Virus Nuclear Antigen 1 function
Authors: Shen Chih-Lung , Liu Cheng-Der , You Ren-In , Ching Yung-Hao , Liang Jun , Ke Liangru , Chen Ya-Lin , Chen Hong-Chi , Hsu Hao-Jen , Liou Je-Wen , Kieff Elliott , Peng Chih-Wen 
Published: February 2016

SignificanceEpstein–Barr Virus (EBV) Nuclear Antigen 1 (EBNA1) is essential for establishing long-term EBV infection in human cells and is implicated in EBV-related malignancies. The maintenance of the EBV genome and viral gene expression from the episome are specifically driven by EBNA1 through binding to origin of plasmid replication (oriP). This study finds that EBNA1 complexes with Ribosome Protein L4 (RPL4) and Nucleolin to stabilize EBNA1 binding to oriP. Cooperation of RPL4’s N terminus with Nucleolin K429 is necessary for EBNA1 oriP binding and episome maintenance, whereas RPL4's C-terminal K380 and K393 induce H3K4me2, which promotes EBNA1 transactivation of oriP. These discoveries enhance our understanding of the complexity of EBNA1’s interactions with host proteins and EBV episomes and reveal new targets for inhibition of EBV genome persistence.
Early and multiple origins of metastatic lineages within primary tumors
Authors: Zhao Zi-Ming , Zhao Bixiao , Bai Yalai , Iamarino Atila , Gaffney Stephen G. , Schlessinger Joseph , Lifton Richard P. , Rimm David L. , Townsend Jeffrey P. 
Published: February 2016

Significance
The knowledge that cancer is an evolutionary process is old, but only recently can sequencing technology provide data for clinically relevant evolutionary analyses of cancer. Approaches developed for evolutionary biology can reveal the relationship among clonal lineages, the ancestral states of gene sequences, and the timing of evolutionary events. We performed whole exome sequencing of cancer tissues from multiple sites of dozens of subjects, demonstrating nonlinear patterns of tumor progression and early origins of metastatic lineages and quantifying the times of occurrence of driver mutations. These findings direct research attention away from the search for genes that induce metastasis toward genes that are mutated early in tumorigenesis, providing therapeutic targets effective against both primary tumors and metastases.
Structure–function analysis of myomaker domains required for myoblast fusion
Authors: Millay Douglas P. , Gamage Dilani G. , Quinn Malgorzata E. , Min Yi-Li , Mitani Yasuyuki , Bassel-Duby Rhonda , Olson Eric N. 
Published: February 2016

Significance
Fusion of myoblasts is required for proper skeletal muscle formation during embryonic development and adult muscle regeneration. Despite the central role for plasma membrane fusion, the molecules and mechanisms that govern this process have remained elusive. Myomaker is the only identified muscle-specific protein required for myoblast fusion; however, the mechanisms by which this multipass membrane protein governs fusion are not understood. Through structure–function analysis and development of cell-based fusion assays, we begin to delineate the domains of the myomaker protein required for fusion.
Kalirin and Trio proteins serve critical roles in excitatory synaptic transmission and LTP
Authors: Herring Bruce E. , Nicoll Roger A. 
Published: February 2016

Significance
Long-term potentiation (LTP), a form of synaptic plasticity that results in the strengthening of glutamatergic synapses, is believed to be the cellular mechanism underlying learning and memory. LTP is induced by calcium influx through NMDA receptors, which in turn activates CaMKII; however, the substrates that CaMKII phosphorylate that ultimately give rise to LTP have been the subject of debate for more than two decades. Here we show that the RhoGEF proteins Kalirin and Trio are the substrates of CaMKII responsible for LTP induction. Furthermore, we show that glutamatergic synapses require Kalirin and Trio, given that such synapses no longer exist in the absence of these proteins.