bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empathy as a “risky strength”: A multilevel examination of empathy and risk for internalizing disorders
Authors: Tone Erin B. , Tully Erin C. 
Published: November 2014

AbstractLearning to respond to others' distress with well-regulated empathy is an important developmental task linked to positive health outcomes and moral achievements. However, this important interpersonal skill set may also confer risk for depression and anxiety when present at extreme levels and in combination with certain individual characteristics or within particular contexts. The purpose of this review is to describe an empirically grounded theoretical rationale for the hypothesis that empathic tendencies can be “risky strengths.” We propose a model in which typical development of affective and cognitive empathy can be influenced by complex interplay among intraindividual and interindividual moderators that increase risk for empathic personal distress and excessive interpersonal guilt. These intermediate states in turn precipitate internalizing problems that map onto empirically derived fear/arousal and anhedonia/misery subfactors of internalizing disorders. The intraindividual moderators include a genetically influenced propensity toward physiological hyperarousal, which is proposed to interact with genetic propensity to empathic sensitivity to contribute to neurobiological processes that underlie personal distress responses to others' pain or unhappiness. This empathic personal distress then increases risk for internalizing problems, particularly fear/arousal symptoms. In a similar fashion, interactions between genetic propensities toward negative thinking processes and empathic sensitivity are hypothesized to contribute to excess interpersonal guilt in response to others' distress. This interpersonal guilt then increases the risk for internalizing problems, especially anhedonia/misery symptoms. Interindividual moderators, such as maladaptive parenting or chronic exposure to parents' negative affect, further interact with these genetic liabilities to amplify risk for personal distress and interpersonal guilt as well as for consequent internalizing problems. Age-related increases in the heritability of depression, anxiety, and empathy-related constructs are consistent with developmental shifts toward greater influence of intraindividual moderators throughout childhood and adolescence, with interindividual moderators exerting their greatest influence during early childhood. Efforts to modulate neurobiological and behavioral expressions of genetic dysregulation liabilities and to promote adaptive empathic skills must thus begin early in development.
Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence
Authors: O'Connor Thomas G. , Moynihan Jan A. , Wyman Peter A. , Carnahan Jennifer , Lofthus Gerry , Quataert Sally A. , Bowman Melissa , Caserta Mary T. 
Published: November 2014

AbstractResearch findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system–brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology.
Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum
Authors: Vaidya Akhil B. , Morrisey Joanne M. , Zhang Zhongsheng , Das Sudipta , Daly Thomas M. , Otto Thomas D. , Spillman Natalie J. , Wyvratt Matthew , Siegl Peter , Marfurt Jutta , Wirjanata Grennady , Sebayang Boni F. , Price Ric N. , Chatterjee Arnab , Nagle Advait , Stasiak Marcin , Charman Susan A. , Angulo-Barturen Iñigo , Ferrer Santiago , Belén Jiménez-Díaz María , Martínez María Santos , Gamo Francisco Javier , Avery Vicky M. , Ruecker Andrea , Delves Michael , Kirk Kiaran , Berriman Matthew , Kortagere Sandhya , Burrows Jeremy , Fan Erkang , Bergman Lawrence W. 
Published: November 2014

AbstractThe quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na+ regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na+ homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na+ homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes.
PHD3 regulates EGFR internalization and signalling in tumours
Authors: Garvalov Boyan K. , Foss Franziska , Henze Anne-Theres , Bethani Ioanna , Gräf-Höchst Sabine , Singh Devendra , Filatova Alina , Dopeso Higinio , Seidel Sascha , Damm Miriam , Acker-Palmer Amparo , Acker Till 
Published: November 2014

AbstractTumours exploit their hypoxic microenvironment to induce a more aggressive phenotype, while curtailing the growth-inhibitory effects of hypoxia through mechanisms that are poorly understood. The prolyl hydroxylase PHD3 is regulated by hypoxia and plays an important role in tumour progression. Here we identify PHD3 as a central regulator of epidermal growth factor receptor (EGFR) activity through the control of EGFR internalization to restrain tumour growth. PHD3 controls EGFR activity by acting as a scaffolding protein that associates with the endocytic adaptor Eps15 and promotes the internalization of EGFR. In consequence, loss of PHD3 in tumour cells suppresses EGFR internalization and hyperactivates EGFR signalling to enhance cell proliferation and survival. Our findings reveal that PHD3 inactivation provides a novel route of EGFR activation to sustain proliferative signalling in the hypoxic microenvironment.
Steatosis inhibits liver cell store-operated Ca2+ entry and reduces ER Ca2+ through a protein kinase C-dependent mechanism
Authors: Wilson Claire H. , Ali Eunüs S. , Scrimgeour Nathan , Martin Alyce M. , Hua Jin , Tallis George A. , Rychkov Grigori Y. , Barritt Greg J. 
Published: November 2014

Lipid accumulation in hepatocytes can lead to non-alcoholic fatty liver disease (NAFLD), which can progress to non-alcoholic steatohepatitis (NASH) and Type 2 diabetes (T2D). Hormone-initiated release of Ca2+ from the endoplasmic reticulum (ER) stores and subsequent replenishment of these stores by Ca2+ entry through SOCs (store-operated Ca2+ channels; SOCE) plays a critical role in the regulation of liver metabolism. ER Ca2+ homoeostasis is known to be altered in steatotic hepatocytes. Whether store-operated Ca2+ entry is altered in steatotic hepatocytes and the mechanisms involved were investigated. Lipid accumulation in vitro was induced in cultured liver cells by amiodarone or palmitate and in vivo in hepatocytes isolated from obese Zucker rats. Rates of Ca2+ entry and release were substantially reduced in lipid-loaded cells. Inhibition of Ca2+ entry was associated with reduced hormone-initiated intracellular Ca2+ signalling and enhanced lipid accumulation. Impaired Ca2+ entry was not associated with altered expression of stromal interaction molecule 1 (STIM1) or Orai1. Inhibition of protein kinase C (PKC) reversed the impairment of Ca2+ entry in lipid-loaded cells. It is concluded that steatosis leads to a substantial inhibition of SOCE through a PKC-dependent mechanism. This enhances lipid accumulation by positive feedback and may contribute to the development of NASH and insulin resistance.
Grammatical Aspect Is a Strength in the Language Comprehension of Young Children With Autism Spectrum Disorder
Authors: Tovar Andrea T. , Fein Deborah , Naigles Letitia R. 
Published: November 2014

Purpose
The comprehension of tense/aspect morphology by children with autism spectrum disorder (ASD) was assessed via Intermodal Preferential Looking (IPL) to determine whether this population's difficulties with producing these morphemes extended to their comprehension.

Method
Four-year-old participants were assessed twice, 4 months apart. They viewed a video that presented side-by-side ongoing and completed events paired with familiar verbs with past tense and progressive morphology. Their eye movements were recorded and coded offline; the IPL measures included percentage of looking time at, and latency of first look to, the matching scene. Spontaneous speech samples were also obtained and coded for number of words, past tense, and progressive inflections.

Results

Relative to their baseline preferences, these 4-year-old children with ASD looked more quickly to and longer at the matching scene for both morphemes. Children who produced more words, including progressive and past morphemes, and those who performed better on standardized language assessments demonstrated better comprehension of –
ing.

Conclusions
Overall, these children with ASD demonstrated consistent comprehension of grammatical aspect morphology; moreover, their degree of comprehension was found to correlate with spontaneous production and standardized test scores.
Silk-based resorbable electronic devices for remotely controlled therapy and in vivo infection abatement
Authors: Tao Hu , Hwang Suk-Won , Marelli Benedetto , An Bo , Moreau Jodie E. , Yang Miaomiao , Brenckle Mark A. , Kim Stanley , Kaplan David L. , Rogers John A. , Omenetto Fiorenzo G. 
Published: November 2014

SignificanceWe present the demonstration of in vivo operation of a subcutaneously implanted, resorbable electronic device. The remotely controlled device was wirelessly activated after implantation, successfully eliminating infection, and subsequently dissolving in the surrounding tissue. This approach is a first step for the development of a class of implantable, technological, biomedical devices that resorb harmlessly, eliminating the need for retrieval after use.
Electrostatic transition state stabilization rather than reactant destabilization provides the chemical basis for efficient chorismate mutase catalysis
Authors: Burschowsky Daniel , van Eerde André , Ökvist Mats , Kienhöfer Alexander , Kast Peter , Hilvert Donald , Krengel Ute 
Published: November 2014

Significance
Chorismate mutase (CM) is a textbook model for enzyme catalysis. Although it promotes a simple unimolecular reaction, the origins of its 2-million–fold rate acceleration have been debated for decades. The relative importance of electrostatic transition state stabilization versus ground state destabilization has been a particularly contentious issue. High-resolution crystallographic snapshots of an engineered CM variant and its complexes with substrate, transition state analog, and product now provide strong experimental evidence that properly positioned active-site charges are essential in this system and that preorganization of the substrate in a reactive conformation contributes relatively little to catalysis. A proper understanding of the role of electrostatics in this and other enzymes is important for ongoing efforts to design new enzymes de novo.
UbcH7 regulates 53BP1 stability and DSB repair
Authors: Han Xiangzi , Zhang Lei , Chung Jinsil , Mayca Pozo Franklin , Tran Amanda , Seachrist Darcie D. , Jacobberger James W. , Keri Ruth A. , Gilmore Hannah , Zhang Youwei 
Published: November 2014

Significance
Double-strand break (DSB) repair sits at the core of genome stability maintenance. Abnormalities in the repair pathway often lead to the development of cancers and resistance to anticancer therapies. Tumor suppressor p53-binding protein 1 (53BP1), a protein critical in regulating DSB repair, is reduced in advanced breast tumors. Furthermore, low levels of 53BP1 correlated with poor prognosis and resistance to chemotherapy. Thus, the protein level of 53BP1 is important for therapeutic response. However, mechanisms regulating 53BP1 protein levels are poorly understood. Here we report a previously unidentified mechanism regulating the protein level of 53BP1, specifically, ubiquitin-conjugating enzyme H7 (UbcH7)-dependent ubiquitination and proteasome-dependent degradation. We further propose an innovative hypothesis that increasing the protein level of 53BP1 enhances the effect of radiotherapy or chemotherapy through suppressing faithful DSB repair.
Collapse of cooperation in evolving games
Authors: Stewart Alexander J. , Plotkin Joshua B. 
Published: November 2014

Significance
This study offers a new perspective on an age-old question: When does cooperation emerge in populations? Two-player games used to study this question produce an array of counterintuitive results. And yet a consensus has emerged that, in an evolving population, cooperation tends to triumph over cheating––through reciprocity and generosity. But, what happens when players can influence not only their tendencies to cooperate, but also the rewards they reap for cooperation? We analyze coevolution of strategies and payoffs and find that, as individuals maximize the benefits of cooperation, they often pave the way for its collapse. Our analysis provides a framework for studying the coevolution of games and strategies, and suggests that maintaining cooperation may be more difficult than previously thought.
Early social exposure in wild chimpanzees: Mothers with sons are more gregarious than mothers with daughters
Authors: Murray Carson M. , Lonsdorf Elizabeth V. , Stanton Margaret A. , Wellens Kaitlin R. , Miller Jordan A. , Goodall Jane , Pusey Anne E. 
Published: November 2014

Significance
Early social experience is critical to developing appropriate adult behavior. Mothers are particularly important social partners but may also facilitate or restrict access to others. Studies investigating human parental facilitation are limited and confounded by culture. Comparative studies therefore provide invaluable insight into how parents provide social opportunities for offspring. We investigated maternal subgrouping patterns by infant sex in one of our closest relatives, chimpanzees, and found that mothers with sons were more gregarious. Infants themselves may influence patterns later in infancy, but differences were apparent early in life, when mothers and infants are in almost constant contact. Furthermore, mothers with sons associated more with adult males, potential behavioral models, early in life. These differences foreshadow sex-typical adult social behavior.
Acquisition of an immunosuppressive protumorigenic macrophage phenotype depending on c-Jun phosphorylation
Authors: Hefetz-Sela Simona , Stein Ilan , Klieger Yair , Porat Rinnat , Sade-Feldman Moshe , Zreik Farid , Nagler Arnon , Pappo Orit , Quagliata Luca , Dazert Eva , Eferl Robert , Terracciano Luigi , Wagner Erwin F. , Ben-Neriah Yinon , Baniyash Michal , Pikarsky Eli 
Published: November 2014

SignificanceTumor-associated macrophages are often associated with poor prognosis, but the molecular cues that impart the change in macrophage phenotypes are mostly unclear. Our findings identify c-Jun N-terminal phosphorylation as a key mediator of macrophage education and point to a recruitment of immunosuppressive regulatory T cells as a possible effector protumorigenic mechanism. This cross-talk between adaptive and innate immune responses occurs before overt tumorigenesis, reversing the classic paradigm of initiation and promotion. Our findings raise the possibility that targeting immune checkpoints could be effective for tumor prevention in chronic inflammatory diseases.
A common brain network links development, aging, and vulnerability to disease
Authors: Douaud Gwenaëlle , Groves Adrian R. , Tamnes Christian K. , Westlye Lars Tjelta , Duff Eugene P. , Engvig Andreas , Walhovd Kristine B. , James Anthony , Gass Achim , Monsch Andreas U. , Matthews Paul M. , Fjell Anders M. , Smith Stephen M. , Johansen-Berg Heidi 
Published: November 2014

Significance
Many evolutionary–developmental models have attempted to relate development and aging, with one popular hypothesis proposing that healthy age-related brain decline mirrors developmental maturation. But this elegant hypothesis has so far lacked clear and direct data to support it. Here, we describe intrinsic, entirely data-driven evidence that healthy brain degeneration and developmental process mirror one another in certain brain regions. Specifically, a data-driven decomposition of structural brain images in 484 healthy participants reveals a network of mainly higher-order regions that develop relatively late during adolescence, demonstrate accelerated degeneration in old age, and show heightened vulnerability to disorders that impact on brain structure during adolescence and aging. These results provide a fundamental link between development, aging, and disease processes in the brain.
Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes
Authors: Mullins Garrett R. , Wang Lifu , Raje Vidisha , Sherwood Samantha G. , Grande Rebecca C. , Boroda Salome , Eaton James M. , Blancquaert Sara , Roger Pierre P. , Leitinger Norbert , Harris Thurl E. 
Published: November 2014

Significance
Adipose tissue maintains metabolic homeostasis during fasting and fed conditions. When nutrients are plentiful, anabolic signaling is mediated by insulin, stimulating adipocytes to take up glucose for energy storage. In the absence of nutrients, catabolic signaling initiates lipolysis, or the release of lipids for energy use, and is mediated by catecholamines. These opposing pathways are evolutionarily conserved and prevent futile cycling, but can lead to metabolic disorders such as insulin resistance if not properly regulated. Here we define a novel mechanism whereby lipolysis inhibits insulin-stimulated glucose uptake in adipocytes. This signaling mechanism likely contributes to insulin resistance when lipolysis is active, such as during high stress or obesity, and this new understanding may lead to novel treatment approaches for hyperglycemia.
Anomalously large isotope effect in the glass transition of water
Authors: Gainaru Catalin , Agapov Alexander L. , Fuentes-Landete Violeta , Amann-Winkel Katrin , Nelson Helge , Köster Karsten W. , Kolesnikov Alexander I. , Novikov Vladimir N. , Richert Ranko , Böhmer Roland , Loerting Thomas , Sokolov Alexei P. 
Published: November 2014

Significance
Water is by far the most important and intriguing liquid. Despite the relative simplicity of its chemical structure there are many puzzling properties of water that remain the focus of active discussions. Our studies revealed an unusually strong isotope effect and an extraordinarily slow temperature variation of the structural relaxation of water at low temperatures. We show that the anomalous behavior of deeply supercooled water is affected by quantum effects, usually considered negligible for the glass transition. However, in water they are significant owing to the small mass of the molecule. The presented results might considerably change our understanding of water dynamics at low temperatures.
Early Holocene chicken domestication in northern China
Authors: Xiang Hai , Gao Jianqiang , Yu Baoquan , Zhou Hui , Cai Dawei , Zhang Youwen , Chen Xiaoyong , Wang Xi , Hofreiter Michael , Zhao Xingbo 
Published: November 2014

Significance
Ancient DNA analysis is a powerful tool to reveal the geographical origins of domesticated species. Here we obtained ancient mtDNA sequences from the earliest archaeological chicken bones from northern China as early as 10,000 y ago. Combined analyses of our ancient sequences with a large dataset of published modern and ancient chicken mtDNA sequences suggest that northern China was likely one of several regions of chicken domestication and provide further insights into the process of human-mediated spread of chickens across the globe. Our results not only suggest that the oldest archaeological chicken bones recovered so far are indeed from ancestors of domestic chickens, but also provide further evidence for one of the earliest, mixed agricultural complexes in the world.
Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis
Authors: Bourgine Paul E. , Scotti Celeste , Pigeot Sebastien , Tchang Laurent A. , Todorov Atanas , Martin Ivan 
Published: November 2014

SignificanceIt has been previously reported that hypertrophic cartilage tissues engineered from human mesenchymal stromal cells can efficiently remodel in vivo into bone organs, recapitulating developmental steps of endochondral ossification. We have here demonstrated that the extracellular matrix (ECM) of such engineered cartilage, even in the absence of a living cell component, retains frankly osteoinductive properties. The use of an apoptosis-driven devitalization technique revealed the importance of preserving the ECM integrity and, in particular, the embedded factors to trigger the regenerative process. Although exemplified in a skeletal context, our work outlines the general paradigm of cell-based but cell-free off-the-shelf materials capable of activating endogenous cells toward the formation of specific tissues.
Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands
Authors: Scheper Jeroen , Reemer Menno , van Kats Ruud , Ozinga Wim A. , van der Linden Giel T. J. , Schaminée Joop H. J. , Siepel Henk , Kleijn David 
Published: November 2014

Significance
Growing concern about bee declines and associated loss of pollination services has increased the urgency to identify the underlying causes. So far, the identification of the key drivers of decline of bee populations has largely been based on speculation. We assessed the relative importance of a range of proposed factors responsible for wild bee decline and show that loss of preferred host plant species is one of the main factors associated with the decline of bee populations in The Netherlands. Interestingly, species foraging on crop plant families have stable or increasing populations. These results indicate that mitigation strategies for loss of wild bees will only be effective if they target the specific host plants of declining bee species.