bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity
Authors: Raheja Radhika , Liu Yuhui , Hukkelhoven Ellen , Yeh Nancy , Koff Andrew 
Published: January 2014

Mutation of the TRIM (tripartite motif)-NHL family members brat and mei-P26 perturb the differentiation of transit-amplifying progenitor cells resulting in tumour-like phenotypes. The NHL (named after the NCL1, HT2A and LIN41 repeat) domain is essential for their growth suppressive activity, and they can induce cell-cycle exit in a RING-independent manner. TRIM3 is the only bona fide tumour suppressor in the mammalian TRIM-NHL subfamily and similar to the other members of this family, its ability to inhibit cell proliferation depends on the NHL domain. However, whether the RING domain was required for TRIM3-dependent cell-cycle exit had not been investigated. In the present study, we establish that the RING domain is required for TRIM3-induced growth suppression. Furthermore, we show that this domain is necessary to promote ubiquitination of p21 in a reconstituted in vitro system where UbcH5a is the preferred E2. Thus the ability of TRIM3 to suppress growth is associated with its ability to ubiquitinate proteins.
Perfect genetic correlation between number of offspring and grandoffspring in an industrialized human population
Authors: Zietsch Brendan P. , Kuja-Halkola Ralf , Walum Hasse , Verweij Karin J. H. 
Published: January 2014

Significance
Reproductive success (offspring quantity) is widely used as a measure of fitness (genetic contribution to future generations). Accurate predictions of the direction and magnitude of evolutionary change using this measure depend on the untested assumption that the genes influencing number of offspring are the same as those influencing number of grandoffspring. Using a population sample of identical and nonidentical Swedish twins and their descendants, we show that the genetic influences on number of offspring and grandoffspring are identical, supporting the use of reproductive success as a measure of fitness in comparable human populations.
Molecular insight into bacterial cleavage of oceanic dimethylsulfoniopropionate into dimethyl sulfide
Authors: Li Chun-Yang , Wei Tian-Di , Zhang Sheng-Hui , Chen Xiu-Lan , Gao Xiang , Wang Peng , Xie Bin-Bin , Su Hai-Nan , Qin Qi-Long , Zhang Xi-Ying , Yu Juan , Zhang Hong-Hai , Zhou Bai-Cheng , Yang Gui-Peng , Zhang Yu-Zhong 
Published: January 2014

Significance
DMS is an important participant in the global sulfur and carbon cycles. DMS oxidation products cause the formation of cloud condensation nuclei and hence may influence weather and climate. DMS is produced through the cleavage of dimethylsulfoniopropionate (DMSP) mainly by marine bacterial DMSP lyases. The molecular mechanism of DMSP cleavage to generate DMS remains unclear. In this study, the crystal structure of DddQ, a DMSP lyase, was solved, and detailed biochemical and structural analyses were performed. Our results also provided a foremost insight into the catalytic mechanism of the DMSP cleavage reaction. This study offers a better understanding of how marine bacteria cleave DMSP to generate the climatically important gas DMS.
Genetic drift opposes mutualism during spatial population expansion
Authors: Müller Melanie J. I. , Neugeboren Beverly I. , Nelson David R. , Murray Andrew W. 
Published: January 2014

Significance
Species expand from where they evolved or migrate in response to climate change. Such spatial expansions can impede mutualistic interactions (beneficial for both partners). Mutualism selects for species coexistence and genetic diversity, but spatial expansion creates regions of low diversity due to repeated founder effects. We show both theoretically and experimentally, using the colony expansion of cross-feeding yeast as a model system, that a critical mutualistic strength is required to “survive” spatial expansions. This constraint may have shaped the evolution of mutualisms, allowing only the spread of very beneficial mutualisms (e.g., the invasion of land by plants with mycorrhizal fungi and flowering plants with pollen-dispersing insects) or leading to additional mechanisms for coordinated partner dispersal (e.g., endosymbionts and lichens).
Environmental enrichment extends ocular dominance plasticity into adulthood and protects from stroke-induced impairments of plasticity
Authors: Greifzu Franziska , Pielecka-Fortuna Justyna , Kalogeraki Evgenia , Krempler Katja , Favaro Plinio D. , Schlüter Oliver M. , Löwel Siegrid 
Published: January 2014

Significance
Experimental animals are usually raised in small, so-called standard cages, depriving them of numerous natural stimuli. We show that raising mice in an enriched environment, allowing enhanced physical, social, and cognitive stimulation, preserved a juvenile brain into adulthood. Enrichment also rejuvenated the visual cortex after extended periods of standard cage rearing and protected adult mice from stroke-induced impairments of cortical plasticity. Because the local inhibitory tone in the visual cortex of adult enriched mice was not only significantly reduced compared with nonenriched animals but at juvenile levels, the plasticity-promoting effect of enrichment is most likely mediated by preserving low juvenile levels of inhibition into adulthood and thereby, extending sensitive phases of enhanced neuronal plasticity into an older age.
Species interactions and the structure of complex communication networks
Authors: Tobias Joseph A. , Planqué Robert , Cram Dominic L. , Seddon Nathalie 
Published: January 2014

Significance
Social signals used in multispecies choruses are generally assumed to be partitioned across temporal, spatial, or design axes to minimize the costs of misidentification. In contrast, we show that Amazonian bird species signaling in temporal and spatial proximity use acoustic signals that are more similar in design than expected by chance. We also show evidence that this pattern emerges because phylogenetically conserved (or potentially convergent) signals mediate interspecific competition among species with similar ecological niches. Together, these results suggest that acoustic choruses can be fundamentally organized by social communication extending beyond species boundaries and that such communication networks are inherently clustered by increased stereotypy and synchrony among species.
Tuberculosis vaccine with high predicted population coverage and compatibility with modern diagnostics
Authors: Knudsen Niels Peter H. , Nørskov-Lauritsen Sara , Dolganov Gregory M. , Schoolnik Gary K. , Lindenstrøm Thomas , Andersen Peter , Agger Else Marie , Aagaard Claus 
Published: January 2014

SignificanceDespite the availability of a number of antibiotics and extensive use of the live vaccine bacillus Calmette–Guérin, tuberculosis remains a major global health problem. Antigen 85 is by far the most popular antigen in current clinical trials vaccines. However, a recent failure of a virus-based vaccine expressing antigen 85 emphasizes the continued need for identifying antigens, testing their protective efficacy, and learning from this process to develop a protective vaccine. The H65 vaccine demonstrates that it is possible to develop antigen 85-free vaccines that does not interfere with current immune-based diagnostic assays.
MAB4-induced auxin sink generates local auxin gradients in
Arabidopsis
organ formation
Authors: Furutani Masahiko , Nakano Yasukazu , Tasaka Masao 
Published: January 2014

Significance
The dynamic auxin transport driven by the auxin efflux carrier PIN-FORMED1 (PIN1) is the key element in organ formation at the shoot apical meristem. Auxin transport during organ formation consists of two distinct types: the convergence of auxin flow at the organ initiation site and the following auxin sink. Our results show that NONPHOTOTROPIC HYPOCOTYL 3-like proteins establish auxin sink, but not auxin convergence, through the control of PIN1 localization. Our study uncovers the molecular mechanism involved in auxin sink and to show its importance in organ development. Besides, we propose a model for polar auxin transport during organ formation, which has the potential to describe on a molecular level the auxin canalization hypothesis.
Engineered temperature compensation in a synthetic genetic clock
Authors: Hussain Faiza , Gupta Chinmaya , Hirning Andrew J. , Ott William , Matthews Kathleen S. , Josić Krešimir , Bennett Matthew R. 
Published: January 2014

Significance
Synthetic gene circuits are often fragile, as perturbations to cellular conditions frequently alter their behavior. This lack of robustness limits the utility of engineered gene circuits and hinders advances in synthetic biology. Here, we demonstrate that environmental sensitivity can be reduced by simultaneously engineering circuits at the protein and network levels. Specifically, we designed and constructed a synthetic genetic clock that exhibits temperature compensation—the clock’s period does not depend on temperature. This feature is nontrivial since biochemical reactions speed up with increasing temperature. To accomplish this goal, we engineered thermal-inducibility into the clock’s regulatory structure. Computational modeling predicted and experiments confirmed that this thermal-inducibility results in a clock with a stable period across a large range of temperatures.
TRAIL-coated leukocytes that kill cancer cells in the circulation
Authors: Mitchell Michael J. , Wayne Elizabeth , Rana Kuldeepsinh , Schaffer Chris B. , King Michael R. 
Published: January 2014

Significance
This paper describes a unique approach to target and kill cancer cells in the bloodstream, in which the extensive surface area of circulating leukocytes is used to display the cancer-specific TNF-related apoptosis inducing ligand (TRAIL) and E-selectin adhesion receptor to the surrounding fluid. The approach is inspired by the cytotoxic activity of natural killer cells and is quite effective at killing cancer cells both in vitro with human blood samples and in mouse blood circulation. The mechanism is surprising and unexpected in that this repurposing of leukocytes in flowing blood is more effective than directly targeting the cancer cells with liposomes or soluble protein.
Mycobacterial mistranslation is necessary and sufficient for rifampicin phenotypic resistance
Authors: Javid Babak , Sorrentino Flavia , Toosky Melody , Zheng Wen , Pinkham Jessica T. , Jain Nina , Pan Miaomiao , Deighan Padraig , Rubin Eric J. 
Published: January 2014

Significance
Although error rates in protein translation, particularly under stress, are high, it is not known if these errors are inherent to the system, or if they may have an adaptive function. Here, we provide evidence that specific mistranslation of mycobacterial proteins is important for phenotypic resistance to the antibiotic rifampicin. This raises the possibility that errors in protein translation play a role in adapting to stress through increasing proteomic diversity.
Earliest evidence for caries and exploitation of starchy plant foods in Pleistocene hunter-gatherers from Morocco
Authors: Humphrey Louise T. , De Groote Isabelle , Morales Jacob , Barton Nick , Collcutt Simon , Bronk Ramsey Christopher , Bouzouggar Abdeljalil 
Published: January 2014

Significance
We present early evidence linking a high prevalence of caries to a reliance on highly cariogenic wild plant foods in Pleistocene hunter-gatherers from North Africa. This evidence predates other high caries populations and the first signs of food production by several thousand years. We infer that increased reliance on wild plants rich in fermentable carbohydrates caused an early shift toward a disease-associated oral microbiota. Systematic harvesting and processing of wild food resources supported a more sedentary lifestyle during the Iberomaurusian than previously recognized. This research challenges commonly held assumptions that high rates of caries are indicative of agricultural societies.
Inflammasome-independent IL-1β mediates autoinflammatory disease in Pstpip2-deficient mice
Authors: Cassel Suzanne L. , Janczy John R. , Bing Xinyu , Wilson Shruti P. , Olivier Alicia K. , Otero Jesse E. , Iwakura Yoichiro , Shayakhmetov Dmitry M. , Bassuk Alexander G. , Abu-Amer Yousef , Brogden Kim A. , Burns Trudy L. , Sutterwala Fayyaz S. , Ferguson Polly J. 
Published: January 2014

SignificanceChronic recurrent multifocal osteomyelitis (CRMO) is a human disorder of the innate immune system that causes bone inflammation that mimics infectious osteomyelitis. There is a spontaneous mutant mouse model of the disease that is caused by homozygous mutations in the genePstpip2. Our studies show that bone inflammation in this model is mediated by the cytokine IL-1β, but that the disease is independent of the nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome and caspase-1, which is different from most other IL-1–mediated disorders. Further, we implicate neutrophils and neutrophil serine proteases in disease pathogenesis. These data provide a rationale for directly targeting the IL-1 receptor or IL-1β as a therapeutic strategy in CRMO.
Critical role for inflammasome-independent IL-1β production in osteomyelitis
Authors: Lukens John R. , Gross Jordan M. , Calabrese Christopher , Iwakura Yoichiro , Lamkanfi Mohamed , Vogel Peter , Kanneganti Thirumala-Devi 
Published: January 2014

Significance
The IL-1 cytokines, IL-1α and IL-1β, are proinflammatory cytokines that are implicated in numerous inflammatory and autoimmune diseases. This study demonstrates that dysregulated immune responses centrally contribute to the pathogenesis of osteomyelitis and identifies a critical role for IL-1β in driving the inflammatory cascade that provokes bone destruction. Caspase-1 activation in the inflammasome complex is the most well established mechanism for IL-1β secretion. Interestingly, inflammasome-independent sources of IL-1β were found to provoke inflammation and osteolytic bone disease. Our findings establish a unique role for inflammasome-independent IL-1β in autoinflammatory bone disease and osteomyelitis, and identify proline–serine–threonine phosphatase interacting protein 2 as a negative regulator of inflammasome-autonomous IL-1β.
Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling
Authors: Shih Yu-Ru V. , Hwang YongSung , Phadke Ameya , Kang Heemin , Hwang Nathaniel S. , Caro Eduardo J. , Nguyen Steven , Siu Michael , Theodorakis Emmanuel A. , Gianneschi Nathan C. , Vecchio Kenneth S. , Chien Shu , Lee Oscar K. , Varghese Shyni 
Published: January 2014

Significance
A mechanistic understanding of how calcium phosphate (CaP) minerals contribute to osteogenic commitment of stem cells and bone tissue formation is a necessary requirement for developing efficient CaP-based synthetic matrices to treat bone defects. This study unravels a previously unknown mechanism, phosphate-ATP-adenosine metabolic signaling, by which the CaP-rich mineral environment in bone tissues promotes osteogenic differentiation of human mesenchymal stem cells. In addition to a mechanical perspective on how biomaterials can influence stem cell differentiation through metabolic pathways, this discovery opens up new avenues for treating critical bone defects and bone metabolic disorders.
Genome-wide evidence of Austronesian–Bantu admixture and cultural reversion in a hunter-gatherer group of Madagascar
Authors: Pierron Denis , Razafindrazaka Harilanto , Pagani Luca , Ricaut François-Xavier , Antao Tiago , Capredon Mélanie , Sambo Clément , Radimilahy Chantal , Rakotoarisoa Jean-Aimé , Blench Roger M. , Letellier Thierry , Kivisild Toomas 
Published: January 2014

Significance
The Mikea are the last known Malagasy population reported to be still practicing a hunter-gatherer lifestyle. Earlier writers thought the Mikea were descended from ancient forager groups who have maintained their way of life up to the present. However, our analyses show that the Mikea are not a remnant population and, to the contrary, derived from a recent admixture of two agriculturalist populations: the Bantu (from Africa) and the Austronesian (from east-Asia). Thus, it is probable that the Mikea have adopted their hunter-gatherer way of life through a recent cultural reversion.
SAD kinases control the maturation of nerve terminals in the mammalian peripheral and central nervous systems
Authors: Lilley Brendan N. , Krishnaswamy Arjun , Wang Zhi , Kishi Masashi , Frank Eric , Sanes Joshua R. 
Published: January 2014

Significance
Synapses between neurons are the primary means by which information flows through the nervous system. The molecular and functional complexity of synapses has been appreciated for some time, but the mechanisms by which synapses assemble remain unclear. We previously identified a conserved pair of signaling proteins, SAD kinases, required for two early events in the formation of axons by developing neurons. Here, we demonstrate that this same pair of signaling molecules acts in a later step to promote the maturation of axonal segments into presynaptic nerve terminals. Thus, SAD kinases may serve to coordinate multiple aspects of neuronal development.
Attosecond vacuum UV coherent control of molecular dynamics
Authors: Ranitovic Predrag , Hogle Craig W. , Rivière Paula , Palacios Alicia , Tong Xiao-Ming , Toshima Nobuyuki , González-Castrillo Alberto , Martin Leigh , Martín Fernando , Murnane Margaret M. , Kapteyn Henry 
Published: January 2014

Significance
We show that we can precisely control molecular dynamics on both nuclear (i.e., femtosecond) and electronic (i.e., attosecond) timescales. By using attosecond vacuum UV light pulse trains that are tunable in the frequency domain, we show that it is possible to switch population between electronically excited states of a neutral molecule on attosecond time scales, and use this ability to coherently control excitation and ionization through specific pathways. This paper represents a milestone advance because almost two decades after attosecond physics was demonstrated, attosecond chemistry has not yet been fully established because the wavelength and bandwidth of attosecond pulses did not well match molecular quantum states. The richness and complexity of the dynamics, even in a simple molecule, is remarkable and daunting.
Human breast cancer metastases to the brain display GABAergic properties in the neural niche
Authors: Neman Josh , Termini John , Wilczynski Sharon , Vaidehi Nagarajan , Choy Cecilia , Kowolik Claudia M. , Li Hubert , Hambrecht Amanda C. , Roberts Eugene , Jandial Rahul 
Published: January 2014

Significance
Breast cancer patients typically develop brain metastases years after their initial diagnosis. During this clinical latency, cancer cells must evolve and adapt to the neural microenvironment to colonize. We hypothesized that breast cancer cells may assume brain-like properties to survive in the brain. Our results suggest that metastases overexpress many variables related to the γ-aminobutyric acid (GABA) and were able to proliferate by metabolizing GABA as a biosynthetic energy source. The expression of brain-like properties by breast cancer cells could be a malignant adaptation required for metastasis to the brain, which could potentially be exploited to develop new therapy for breast cancer patients.
p85α deficiency protects β-cells from endoplasmic reticulum stress-induced apoptosis
Authors: Winnay Jonathon N. , Dirice Ercument , Liew Chong Wee , Kulkarni Rohit N. , Kahn C. Ronald 
Published: January 2014

Significance
In type 2 diabetes, peripheral insulin resistance challenges the pancreatic β-cell to augment insulin synthesis and secretion. This compensatory mechanism eventually fails due to β-cell dysfunction, an increase in β-cell apoptosis, and a resultant decrease in β-cell mass. One mechanism contributing to this decline in β-cell mass is the development of endoplasmic reticulum (ER) stress. We have elucidated a role for the p85α regulatory subunit of PI3K as a modulator of ER stress-dependent apoptosis in β-cells by virtue of its ability to positively regulate the proapoptotic actions of x-box binding protein 1. The ablation of p85α specifically in the β-cell in a mouse model of ER stress-dependent β-cell apoptosis delays the decline in β-cell mass and subsequent development of diabetes.
Loss of liver E-cadherin induces sclerosing cholangitis and promotes carcinogenesis
Authors: Nakagawa Hayato , Hikiba Yohko , Hirata Yoshihiro , Font-Burgada Joan , Sakamoto Kei , Hayakawa Yoku , Taniguchi Koji , Umemura Atsushi , Kinoshita Hiroto , Sakitani Kosuke , Nishikawa Yuji , Hirano Kenji , Ikenoue Tsuneo , Ijichi Hideaki , Dhar Debanjan , Shibata Wataru , Akanuma Masao , Koike Kazuhiko , Karin Michael , Maeda Shin 
Published: January 2014

Significance
The precise roles of E-cadherin in the liver and liver carcinogenesis are still unknown. Here we show that mice lacking E-cadherin in the liver develop spontaneous periportal inflammation via an impaired intrahepatic biliary network, as well as periductal fibrosis, which resembles primary sclerosing cholangitis. Inducible gene knockout studies identified E-cadherin loss in biliary epithelial cells as a causal factor of cholangitis induction, and dysregulated E-cadherin expression was also seen in patients with primary sclerosing cholangitis. E-cadherin loss also significantly accelerates genetically and chemically engineered liver cancer through epithelial–mesenchymal transition, up-regulation of stem cell markers, and ERK activation. Thus, E-cadherin plays critical roles in maintaining homeostasis and suppressing carcinogenesis in the liver.
The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified
Authors: Movérare-Skrtic Sofia , Börjesson Anna E. , Farman Helen H. , Sjögren Klara , Windahl Sara H. , Lagerquist Marie K. , Andersson Annica , Stubelius Alexandra , Carlsten Hans , Gustafsson Jan-Åke , Ohlsson Claes 
Published: January 2014

Significance
Estrogen exerts important effects in the skeleton, which are primarily mediated via estrogen receptor (ER)α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. Previous studies demonstrate that ERα ligands might act as agonists, partial agonists, or antagonists. We demonstrate that the ERα antagonist ICI 182,780 (ICI) acts in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. Importantly, ICI exerted a pronounced inverse agonistic activity in the growth plate of mice lacking ERαAF-2. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist.