bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-molecule imaging and kinetic analysis of cooperative cofilin–actin filament interactions
Authors: Hayakawa Kimihide , Sakakibara Shotaro , Sokabe Masahiro , Tatsumi Hitoshi 
Published: June 2014

Significance
Cooperative protein–protein interactions are essential for understanding the regulation of enzymes. However, the dynamic interactions that endow proteins with cooperativity in solution have not been directly imaged and analyzed. In this study, we performed super-high-resolution real-time single-molecule imaging of the binding of cofilin to single actin filaments and its subsequent detachment. Results show that long-term binding (>0.4 s) of a single cofilin molecule enhances the binding of additional cofilin within 65 nm (across 24 actin subunits) of the initial binding site. This cooperative binding is presumed to be crucial for the peculiar actin filament-severing action of cofilin.
Contact between bird species of different lifespans can promote the emergence of highly pathogenic avian influenza strains
Authors: Wikramaratna Paul S. , Pybus Oliver G. , Gupta Sunetra 
Published: June 2014

Significance
The emergence of highly pathogenic avian influenza viruses has received much attention due to the severe consequences of their occasional spread to humans, as well as the large toll they take on the poultry industry. Here we argue that the main barriers to the emergence of these viruses are imposed by immunity to related strains rather than the ability of the virus to acquire the necessary mutations. We show that, under these circumstances, patterns of influenza in different avian species are strongly dependent on their lifespan and that processes that alter the interactions between species of different lifespans—such as changes in farming practices—could promote the emergence of highly pathogenic types.
Activation of Ras overcomes B-cell tolerance to promote differentiation of autoreactive B cells and production of autoantibodies
Authors: Teodorovic Lenka S. , Babolin Chiara , Rowland Sarah L. , Greaves Sarah A. , Baldwin David P. , Torres Raul M. , Pelanda Roberta 
Published: June 2014

Significance
Only a fraction of immature B cells enter the mature B-cell pool to produce antibodies. Autoreactive immature B cells expressing antibodies to self remain in the bone marrow to continue immunoglobulin gene rearrangements and are selected into the periphery only if they eliminate their autoreactive specificity. We show that the rat sarcoma (Ras)-Erk pathway, which leads to the generation of mature B cells, is not constitutively activated in autoreactive immature B cells. Furthermore, activation of Ras can alter the selection pattern of autoreactive cells, inhibiting immunoglobulin gene recombination via PI3K, promoting cell differentiation via Erk, and resulting in secretion of autoantibodies. This suggests that changes in the activation of the Ras–Erk/PI3K pathway have the potential to lead to autoimmune manifestations.
mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress
Authors: Grahammer Florian , Haenisch Nora , Steinhardt Frederic , Sandner Lukas , Roerden Malte , Arnold Frederic , Cordts Tomke , Wanner Nicola , Reichardt Wilfried , Kerjaschki Dontscho , Ruegg Markus A. , Hall Michael N. , Moulin Pierre , Busch Hauke , Boerries Melanie , Walz Gerd , Artunc Ferruh , Huber Tobias B. 
Published: June 2014

Significance
Mammalian target of rapamycin complex 1 (mTORC1) inhibitors are commonly used as immunosuppressants in solid-organ transplantation and as antiproliferative agents in various cancers. Despite indications of serious renal adverse events caused by mTORC1 inhibition, the role of mTORC1 for renal epithelial function and homeostasis has remained elusive. Unexpectedly, tubular mTORC1 controls energy-driven urine-concentrating mechanisms by maintaining mitochondrial biogenesis. Under pathophysiological conditions, mTORC1-dependent mitochondrial biogenesis is essential for energy supply and adaptation in response to ischemia. These findings identify mTORC1 as an important regulator of tubular energy metabolism, transcellular transport processes, and ischemic stress responses.
Ferroelectric switching of elastin
Authors: Liu Yuanming , Cai Hong-Ling , Zelisko Matthew , Wang Yunjie , Sun Jinglan , Yan Fei , Ma Feiyue , Wang Peiqi , Chen Qian Nataly , Zheng Hairong , Meng Xiangjian , Sharma Pradeep , Zhang Yanhang , Li Jiangyu 
Published: June 2014

Significance
Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present, to our knowledge, the first macroscopic observation of ferroelectric switching in a biological system, and we elucidate the origin and mechanism underpinning ferroelectric switching of elastin. It is discovered that the polarization in elastin is intrinsic at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics. Our findings settle a long-standing question on ferroelectric switching in biology and establish ferroelectricity as an important biophysical property of proteins. We believe this is a critical first step toward resolving its physiological significance and pathological implications.
Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs
Authors: Nguyen Giang Huong , Tang Weiliang , Robles Ana I. , Beyer Richard P. , Gray Lucas T. , Welsh Judith A. , Schetter Aaron J. , Kumamoto Kensuke , Wang Xin Wei , Hickson Ian D. , Maizels Nancy , Monnat Raymond J. , Harris Curtis C. 
Published: June 2014

Significance
Bloom syndrome is a rare human genetic disease characterized by proportional dwarfism, immunodeficiency, and an elevated risk of many different cancer types. We used RNA expression profiling to identify networks of mRNAs and microRNAs that are differentially expressed in cells from Bloom syndrome patients and associated with cell proliferation, survival, and molecular pathways promoting cancer. Altered mRNA expression was in some cases strongly correlated with the presence of G4 motifs, which may form G-quadruplex targets that are bound by BLM. Further analysis of the genetic networks we identified may elucidate mechanisms responsible for Bloom syndrome disease pathogenesis and ways to ameliorate or prevent disease in affected individuals.
Double electron–electron resonance reveals cAMP-induced conformational change in HCN channels
Authors: Puljung Michael C. , DeBerg Hannah A. , Zagotta William N. , Stoll Stefan 
Published: June 2014

Significance
Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels play central roles in the heart and the brain. In the heart, they are present in pacemaker cells and contribute to the regulation of the heartbeat. In the brain, they are involved in electrical signaling of neurons. HCN channels are activated by hyperpolarization of the cell membrane and are regulated by binding of cAMP to a site in an intracellular binding domain. This study shows that this binding domain undergoes major structural changes upon binding of cAMP. The results are the first step toward elucidating the molecular mechanism of gating in this important class of ion channels.
Fluid flows created by swimming bacteria drive self-organization in confined suspensions
Authors: Lushi Enkeleida , Wioland Hugo , Goldstein Raymond E. 
Published: June 2014

Significance
The collective dynamics of swimming microorganisms exhibits a complex interplay with the surrounding fluid: the motile cells stir the fluid, which in turn can reorient and advect them. This feedback loop can result in long-range interactions between the cells, an effect whose significance remains controversial. We present a computational model that takes into account these cell–fluid interactions and cell–cell forces and that predicts counterintuitive cellular order driven by long-range flows. This prediction is confirmed with experimental studies that track the orientation of cells in a confined, dense bacterial suspension.
Piezo1, a mechanically activated ion channel, is required for vascular development in mice
Authors: Ranade Sanjeev S. , Qiu Zhaozhu , Woo Seung-Hyun , Hur Sung Sik , Murthy Swetha E. , Cahalan Stuart M. , Xu Jie , Mathur Jayanti , Bandell Michael , Coste Bertrand , Li Yi-Shuan J. , Chien Shu , Patapoutian Ardem 
Published: June 2014

Significance
Ion channels that are activated by mechanical force have been implicated in numerous physiological systems. In mammals, the identity of these channels remains poorly understood. We recently described Piezos as evolutionarily conserved mechanically activated ion channels and showed that Piezo2 is required for activation of touch receptors in the skin. Here we show that Piezo1 is a critical component of endothelial cell mechanotransduction and is required for embryonic development. Piezo1 is expressed in embryonic endothelial cells and is activated by fluid shear stress. Loss of Piezo1 affects the ability of endothelial cells to alter their alignment when subjected to shear stress. These results suggest a potential role for Piezo1 in mechanotransduction in adult cardiovascular function and disease.
Personal Network Characteristics of Youth in Substance use Treatment: Motivation for and Perceived Difficulty of Positive Network Change
Authors: Chung Tammy , Sealy Lauren , Abraham Margaret , Ruglovsky Cynthia , Schall Jacqueline , Maisto Stephen A. 
Published: June 2014

Background Among youth in substance use treatment, peer substance use consistently predicts worse treatment outcomes. This study characterized personal (egocentric) networks of treated youth and examined predictors of adolescents’ motivation and perceived difficulty in making changes in the peer network to support recovery. Methods Adolescents (aged 14–18; N = 155) recruited from substance use treatment reported on substance use severity, motivation to abstain from substance use, abstinence goals such as “temporary abstinence,” motivation and perceived difficulty in reducing contact with substance-using peers, and personal network characteristics. Personal network variables included composition (proportion of abstinent peers) and structure (number of network members, extent of ties among members) for household and nonhousehold (peer) members. Results Although a majority of peer network members were perceived as using alcohol or marijuana, youth in treatment had relatively high motivation to abstain from substance use. However, treated youths’ motivation to reduce contact with substance-using peers was relatively low. In particular, a goal of temporary abstinence was associated with lower motivation to change the peer network. For marijuana, specifically, network composition features (proportion of abstinent peers) were associated with motivation and perceived difficulty to change the peer network. For marijuana, in particular, network structural variables (extent of ties among members) were associated only with perceived difficulty of changing the peer network. Conclusions Despite high motivation to abstain from substance use during treatment, adolescents reported low motivation to reduce contact with substance-using peers. Personal motivation to abstain and abstinence goal predicted motivation to reduce contact with substance-using peers. In contrast, particularly for marijuana, network structure predicted perceived difficulty of network change. Results highlight the potential utility of addressing motivation and perceived difficulty to change the peer network as part of youth network-based interventions.
Latino Immigrants’ Biological Parents’ Histories of Substance use Problems in Their Country of Origin Predict Their Pre- and Post-Immigration Alcohol use Problems
Authors: Blackson Timothy C. , De La Rosa Mario , Sanchez Mariana , Li Tan 
Published: June 2014

Background No studies to date have assessed whether recent young adult (aged 18–34) Latino immigrants’ biological parents’ histories of substance use problems (BPHSUP) in their country of origin predict their alcohol use problems at pre- and post-immigration to the United States (US). Methods BPHSUP in their country of origin were assessed via interviews conducted by bilingual Latino researchers with recent Latino immigrants primarily from Cuba and Central and South America recruited through respondent-driven sampling at the time of their immigration to southeastern US. Three waves of data were collected to document Latino immigrants’ severity of alcohol use problems at pre-immigration and 2 annual post-immigration follow-up assessments. BPHSUP+/− status was used as a predictor of Latinos’ ( N = 452; 45.8% female, 54.2% male) Alcohol Use Disorders Identification Test (AUDIT) scores at pre- and post-immigration with age, education, and income as covariates as wells as odds ratios for AUDIT classifications of hazardous use, harmful use, and dependence. Results BPHSUP+ status predicted Latino immigrants’ higher AUDIT scores pre- and post-immigration by gender ( P < .01) compared with Latino immigrants of BPHSUP− status, controlling for age, education, and income. BPHSUP+ status predicted odds ratios of 3.45 and 2.91 for AUDIT alcohol dependence classification for men and women, respectively. Conclusions This study documents that BPHSUP+/− status in their country of origin predict their young adult Latino offspring's severity of alcohol use problems pre- and post-immigration. These results may inform (1) community-based health care providers to screen recent young adult Latino immigrants for their BPHSUP+/− status and severity of alcohol use problems to redirect trajectories away from alcohol use disorders toward more normative post-immigration outcomes through culturally relevant prevention services and (2) future research advantages of differential susceptibility theory. Implications for future research and the need for replication studies in other geographic regions of the US are discussed.
PIWI proteins and their interactors in piRNA biogenesis, germline development and gene expression
Authors: Ku Hsueh-Yen , Lin Haifan 
Published: June 2014

AbstractPIWI-interacting RNAs (piRNAs) are a complex class of small non-coding RNAs that are mostly 24–32 nucleotides in length and composed of at least hundreds of thousands of species that specifically interact with the PIWI protein subfamily of the ARGONAUTE family. Recent studies revealed that PIWI proteins interact with a number of proteins, especially the TUDOR-domain-containing proteins, to regulate piRNA biogenesis and regulatory function. Current research also provides evidence that PIWI proteins and piRNAs are not only crucial for transposon silencing in the germline, but also mediate novel mechanisms of epigenetic programming, DNA rearrangements, mRNA turnover, and translational control both in the germline and in the soma. These new discoveries begin to reveal an exciting new dimension of gene regulation in the cell.
Pathophysiology of Celiac Disease
Authors: Koning Frits 
Published: June 2014

ABSTRACTCeliac disease (CD) is strongly associated with HLA‐DQ2 and HLA‐DQ8, HLA‐class II molecules that present antigen‐derived peptides to CD4 T cells. Indeed, proinflammatory CD4 T cells specific for gluten‐derived peptides bound to HLA‐DQ2 or HLA‐DQ8 are present in the lamina propria of patients, and not found in nonceliac controls. While gluten peptides bind poorly to HLA‐DQ2/8, modification by tissue tranglutaminase converts the neutral amino acid glutamine into glutamic acid, introducing a negative charge that allows high affinity binding. Thus, the association between CD and HLA‐DQ2/8 is well understood. What is less clear is why only a small minority of HLA‐DQ2/8 positive individuals develops CD, why disease can develop at any stage in life and present with highly variable symptoms. I discuss this in the framework of the multiple hit model: next to genetic predisposition, multiple other factors—some extrinsic, some intrinsic—can favour or protect from disease development.
Celiac Disease and Autoimmunity
Authors: Troncone Riccardo , Discepolo Valentina 
Published: June 2014

ABSTRACTCeliac disease (CD) has a multifactorial etiology with complex genetics and frequently occurs in association with other autoimmune disorders. Even though triggered by a dietary antigen, it shows many autoimmune features, the most peculiar being the presence of high titers of anti‐tissue transglutaminase 2 autoantibodies, produced in the small intestinal mucosa since the early stages of the disease. More than 60% of CD‐associated susceptibility loci are shared with at least another autoimmune condition, suggesting common pathogenic mechanisms. In particular, recognition of peptides by HLA molecules, posttranslational modifications required for optimal peptide binding and immune mechanisms leading to tissue damage have been found in CD as well as in other autoimmune diseases. This review briefly summarizes the main autoimmune features of CD, underlining the similarities with other autoimmune disorders, in particular with type 1 diabetes mellitus. Furthermore, the role of gluten and microbiome in driving autoimmunity is discussed.
Plasma Membrane Localization Is Essential for Oryza sativa Pto-Interacting Protein 1a-Mediated Negative Regulation of Immune Signaling in Rice
Authors: Matsui Hidenori , Fujiwara Masayuki , Hamada Satoshi , Shimamoto Ko , Nomura Yuko , Nakagami Hirofumi , Takahashi Akira , Hirochika Hirohiko 
Published: June 2014

Abstract
Oryza sativa Pto-interacting protein 1a (OsPti1a), an ortholog of tomato (Solanum lycopersicum) SlPti1, functions as a negative regulator of innate immunity in rice (Oryza sativa). In ospti1a mutants, the activation of immune responses, including hypersensitive response-like cell death, is caused by loss of the OsPti1a protein; however, it is as yet unclear how OsPti1a suppresses immune responses. Here, we report that OsPti1a localizes to detergent-resistant membrane fractions of the plasma membrane through lipid modification of the protein’s amino terminus, which is highly conserved among Pti1 orthologs in several plant species. Importantly, mislocalization of OsPti1a after deletion of its amino terminus reduced its ability to complement the mutant phenotypes, including hypersensitive response-like cell death. Furthermore, complex formation of OsPti1a depends on its amino terminus-mediated membrane localization. Liquid chromatography-tandem mass spectrometry analysis of OsPti1a complex-interacting proteins identified several defense-related proteins. Collectively, these findings indicate that appropriate complex formation by OsPti1a at the plasma membrane is required for the negative regulation of plant immune responses in rice.
Burning for biodiversity: highly resilient ant communities respond only to strongly contrasting fire regimes in Australia's seasonal tropics
Authors: Andersen Alan N. , Ribbons Relena R. , Pettit Magen , Parr Catherine L. 
Published: June 2014

Summary

According to the pyrodiversity paradigm, a wide range of fire regimes is required to maintain biodiversity in fire‐prone landscapes. However, the requisite level of pyrodiversity has seldom been tested and may actually be very low.

Here, we examine the sensitivity of tropical savanna ants to variation in fire regimes using results from a long‐term fire experiment near Darwin, Australia. Six experimental fire regimes, with varying fire frequency and seasonality, have been applied to 18 one‐ha plots in three replicated blocks since 2004, with ants sampled prior to experimental burning and then annually after up to 2009. Our primary focus is on the extent to which different patterns of ant richness and composition are associated with each of the six treatment regimes, or whether there is such high overlap that differences only become apparent when experimental treatments are grouped to provide strongly contrasting fire regimes.

When treating each of the six fire treatments separately, we were unable to detect a significant influence of fire on any ant community response variable. We were only able to detect significant ant responses when we grouped the experimental treatments into two contrasting fire frequency classes, low (burnt at most once over the 5 years) vs. high (burnt every 1 or 2 years). Even then, these responses were only evident after 3 years of fire treatment.

Our findings demonstrate that ant communities have very high resilience in relation to fire, with differences evident only between strongly contrasting regimes. Such resilience appears to be characteristic of savanna ants throughout the world.

Synthesis and applications. A large range of finely tuned fire regimes is unlikely to promote regional ant diversity. Rather, only very limited pyrodiversity (a combination of frequently and infrequently burnt areas) would appear to be sufficient for maintaining diversity at a landscape scale. It is important that fire management for biodiversity conservation focuses on the demonstrated requirements of target species, rather than be based on an assumption that ‘pyrodiversity begets biodiversity’.
Testing predictions of the Janzen–Connell hypothesis: a meta‐analysis of experimental evidence for distance‐ and density‐dependent seed and seedling survival
Authors: Comita Liza S. , Queenborough Simon A. , Murphy Stephen J. , Eck Jenalle L. , Xu Kaiyang , Krishnadas Meghna , Beckman Noelle , Zhu Yan 
Published: June 2014

Summary

The Janzen–Connell hypothesis proposes that specialist natural enemies, such as herbivores and pathogens, maintain diversity in plant communities by reducing survival rates of conspecific seeds and seedlings located close to reproductive adults or in areas of high conspecific density. Variation in the strength of distance‐ and density‐dependent effects is hypothesized to explain variation in plant species richness along climatic gradients, with effects predicted to be stronger in the tropics than the temperate zone and in wetter habitats compared to drier habitats.

We conducted a comprehensive literature search to identify peer‐reviewed experimental studies published in the 40+ years since the hypothesis was first proposed. Using data from these studies, we conducted a meta‐analysis to assess the current weight of evidence for the distance and density predictions of the Janzen–Connell hypothesis.

Overall, we found significant support for both the distance‐ and density‐dependent predictions. For all studies combined, survival rates were significantly reduced near conspecifics compared to far from conspecifics, and in areas with high densities of conspecifics compared to areas with low conspecific densities. There was no indication that these results were due to publication bias.

The strength of distance and density effects varied widely among studies. Contrary to expectations, this variation was unrelated to latitude, and there was no significant effect of study region. However, we did find a trend for stronger distance and density dependence in wetter sites compared to sites with lower annual precipitation. In addition, effects were significantly stronger at the seedling stage compared to the seed stage.

Synthesis. Our study provides support for the idea that distance‐ and density‐dependent mortality occurs in plant communities world‐wide. Available evidence suggests that natural enemies are frequently the cause of such patterns, consistent with the Janzen–Connell hypothesis, but additional studies are needed to rule out other mechanisms (e.g. intraspecific competition). With the widespread existence of density and distance dependence clearly established, future research should focus on assessing the degree to which these effects permit species coexistence and contribute to the maintenance of diversity in plant communities.