bluuebunny/crossref_metadata_2025_split huggingface dataset:
Watching individual molecules flex within lipid membranes using SERS
Authors: Taylor Richard W. , Benz Felix , Sigle Daniel O. , Bowman Richard W. , Bao Peng , Roth Johannes S. , Heath George R. , Evans Stephen D. , Baumberg Jeremy J. 
Published: August 2014

AbstractInterrogating individual molecules within bio-membranes is key to deepening our understanding of biological processes essential for life. Using Raman spectroscopy to map molecular vibrations is ideal to non-destructively ‘fingerprint’ biomolecules for dynamic information on their molecular structure, composition and conformation. Such tag-free tracking of molecules within lipid bio-membranes can directly connect structure and function. In this paper, stable co-assembly with gold nano-components in a ‘nanoparticle-on-mirror’ geometry strongly enhances the local optical field and reduces the volume probed to a few nm3, enabling repeated measurements for many tens of minutes on the same molecules. The intense gap plasmons are assembled around model bio-membranes providing molecular identification of the diffusing lipids. Our experiments clearly evidence measurement of individual lipids flexing through telltale rapid correlated vibrational shifts and intensity fluctuations in the Raman spectrum. These track molecules that undergo bending and conformational changes within the probe volume, through their interactions with the environment. This technique allows for in situ high-speed single-molecule investigations of the molecules embedded within lipid bio-membranes. It thus offers a new way to investigate the hidden dynamics of cell membranes important to a myriad of life processes.
Bloom of the cyanobacterium Moorea bouillonii on the gorgonian coral Annella reticulata in Japan
Authors: Yamashiro Hideyuki , Isomura Naoko , Sakai Kazuhiko 
Published: August 2014

AbstractCoral populations are in decline due to environmental changes and biological attacks by predators and infectious diseases. Here, we report a localized bloom of the benthic filamentous cyanobacterium Moorea bouillonii (formerly Lyngbya bouillonii) observed exclusively on the gorgonian (sea fan) coral Annella reticulata at around 20 m depth in Japan. The degree of infection has reached 26% among different sizes of Annella colonies. Thick and continuous growth of Moorea may be sustained partly by symbiotic alpheid shrimp, which affix Moorea filaments to gorgonian corals for use as food and shelter. Most filaments get entangled on the coral colony, some penetrate into the stem of the coral with a swollen end like a root hair, which appears to function as an anchor in Annella. In addition to the cyanobacterium–shrimp interaction, the new trait of anchoring by the cyanobacterium into gorgonian coral may contribute to persistence of this bloom.
Exome sequencing identifies frequent mutation of MLL2 in non–small cell lung carcinoma from Chinese patients
Authors: Yin Shanye , Yang Jing , Lin Bin , Deng Wenjun , Zhang Yuchao , Yi Xianfu , Shi Yufang , Tao Yong , Cai Jun , Wu Chung-I , Zhao Guoping , Hurst Laurence D. , Zhang Jie , Hu Landian , Kong Xiangyin 
Published: August 2014

AbstractLung cancer is the most common cause of cancer mortality worldwide, with an estimated 1.4 million deaths each year. Here we report whole-exome sequencing of nine tumor/normal tissue pairs from Chinese patients with non-small cell lung carcinoma (NSCLC). This allows us to identify a number of significantly mutated genes in NSCLC, which were highly enriched in DNA damage repair, NF-κB pathway, JAK/STAT signaling and chromatin modification. Notably, we identify a histone-lysine methyltransferase gene, namely, MLL2, as one of the most significantly mutated genes in our screen. In a following validation study, we identify deleterious mutations of MLL2 in 12 out of 105 (11.4%) NSCLC patients. Additionally, reduced or lost expression of MLL2 was commonly observed in tumor tissues as compared with paired adjacent non-tumor tissues regardless of mutation status. Together, our study defines the landscape of somatic mutations in Chinese NSCLC and supports the role of MLL2 mutation in the pathogenesis of the disease.
Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus
Authors: Yang Yang , Du Lanying , Liu Chang , Wang Lili , Ma Cuiqing , Tang Jian , Baric Ralph S. , Jiang Shibo , Li Fang 
Published: August 2014

Significance
A constant and long-term threat to human health is cross-species transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) from bats to humans. However, this process is poorly understood. Examining the cross-species transmissibility of bat coronavirus HKU4, which is genetically related to MERS-CoV, can provide critical information about the likely causes of MERS-CoV infections in humans. Here we investigate the receptor usage and cell entry mechanism of HKU4 compared with MERS-CoV. Our results reveal that MERS-CoV has adapted to use human receptor and cellular proteases for efficient human cell entry, whereas HKU4 can potentially follow-up and also infect human cells. These findings are critical for evaluating emerging disease potentials of bat coronaviruses and for preventing and controlling their spread in humans.
Characterizing the proton loading site in cytochromecoxidase
Authors: Lu Jianxun , Gunner M. R. 
Published: August 2014

SignificanceThe transmembrane proton gradient is the primary source of cellular energy. Cytochromecoxidase pumps protons uphill across the membrane using the energy released by the reduction of O2. Proton transport requires that residues change their proton affinity during the reaction cycle. Calculation of proton binding identifies a cluster of residues that bind and release a proton on each reduction of the active site. These residues can constitute a proton loading site. The heme propionic acids play the central role in proton loading. If the propionic acid proton affinity is too low, no protons will be loaded. The same proton-pumping mechanism can be used for each of the four redox steps carried out in the reaction cycle.
Vectored antibody gene delivery protects againstPlasmodium falciparumsporozoite challenge in mice
Authors: Deal Cailin , Balazs Alejandro B. , Espinosa Diego A. , Zavala Fidel , Baltimore David , Ketner Gary 
Published: August 2014

SignificanceMalaria caused byPlasmodium falciparumresults in the death of between 500,000 and 800,000 children per year and thus presents a major infectious disease threat to public health. Antibodies directed against the circumsporozoite protein of the infectious form of the parasite can preventP. falciparuminfection. Nevertheless, current candidate malaria vaccines do not elicit consistent, durable protection. Here we demonstrate that an alternative to conventional immunization, antibody gene delivery by a viral vector [vectored immunoprophylaxis (VIP)], can direct sustained expression of protective mAb in vivo and preventP. falciparuminfection in a rodent model. These studies provide a proof of principle for the use of VIP against the deadliest form of human malaria.
Demography, not inheritance, drives phenotypic change in hunted bighorn sheep
Authors: Traill Lochran W. , Schindler Susanne , Coulson Tim 
Published: August 2014

Significance
Understanding the consequences that selective harvest has on a targeted trait, such as body size, is a great challenge. This is principally because it is difficult to evaluate the relative importance of the evolutionary and demographic factors that underlie a change in the distribution of a selected trait in a hunted population. Here we use a novel and recently developed two-sex integral projection model to tease apart the underlying demographic and evolutionary mechanisms of trait change in a trophy-hunted bighorn sheep population. We find that body size is weakly inherited and that subsequently demographic change, and not evolutionary change, as previously thought, is the principle driver of trait shifts in hunted bighorn sheep.
Drought stress variability in ancient Near Eastern agricultural systems evidenced by δ
13
C in barley grain
Authors: Riehl Simone , Pustovoytov Konstantin E. , Weippert Heike , Klett Stefan , Hole Frank 
Published: August 2014

Significance
Collapse and resilience of ancient Near Eastern societies is intrinsically tied to agricultural production. Despite intensive palaeoclimate research, the role of environmental conditions in ancient agricultural production is little understood. Stable carbon isotope analysis on cereal grains from archaeological sites provides a direct evidence for drought stress. This paper demonstrates that drought stress correlated with major climatic fluctuations and affected many agricultural settlements in the ancient Near East but that its regional impact was diverse and influenced by geographic factors and human technology. The results lead to a better understanding of how ancient agricultural societies performed under fluctuating climate and regionally diverse environmental conditions.
Hybrid biosynthetic gene therapy vector development and dual engineering capacity
Authors: Jones Charles H. , Ravikrishnan Anitha , Chen Mingfu , Reddinger Ryan , Kamal Ahmadi Mahmoud , Rane Snehal , Hakansson Anders P. , Pfeifer Blaine A. 
Published: August 2014

Significance
Vaccination is a powerful means of preempting or treating disease. The process depends on successful recognition of a foreign entity (an antigen) to elicit a strong immune response. The delivery of an antigen encoded as a DNA molecule (a genetic antigen) requires the assistance of a vector to facilitate the process of gene expression within immune system sentinels termed antigen-presenting cells (APCs). In this study, two normally distinct vectors (a bacterial cell and a synthetic polymer) were combined to generate a hybrid vector. The new vector coupled synergistic mechanisms to assist and improve gene delivery to APCs. Furthermore, the hybrid vector provides unique and complimentary engineering capabilities that were demonstrated to tailor and improve APC gene delivery further.
Rare earth elements activate endocytosis in plant cells
Authors: Wang Lihong , Li Jigang , Zhou Qing , Yang Guangmei , Ding Xiao Lan , Li Xiaodong , Cai Chen Xin , Zhang Zhao , Wei Hai Yan , Lu Tian Hong , Deng Xing Wang , Huang Xiao Hua 
Published: August 2014

Significance
Because of their promotional effects on plant growth and development, rare earth elements (REEs) have been widely used in agriculture as plant growth stimulants. However, little is known about the cellular basis of REE actions in plants, and the biological safety of farm REE application in agriculture has not yet attracted enough attention. Here, we show that two types of REEs entered plant cells by endocytosis, and that they both had an activating effect on endocytosis. Moreover, we found that a portion of REEs was finally deposited in plant cells. Our data thus provide novel insights into the cellular mechanisms of REE actions in plants, and may also serve as valuable documentation for evaluating the biological safety of REE application in agriculture.
Legislating Incentives for Attorney Representation in Civil Rights Litigation
Authors: Farhang Sean , Spencer Douglas M. 
Published: August 2014

AbstractCongress routinely relies on private lawsuits to enforce its mandates. In this article, we investigate whether, when it does so, the details of the legislation can importantly influence the extent to which the private bar is mobilized to carry out the prosecutorial function. Using an original and novel data set based on review of archived litigation documents for cases filed in the Northern and Eastern Districts of California over the two decades spanning 1981–2000, we examine the effects of the Civil Rights Act of 1991, which increased economic damages available to Title VII job discrimination plaintiffs, on their ability to secure counsel. We find that over the course of the decade after passage, the law substantially increased the probability that Title VII plaintiffs would be represented by counsel and that in doing so it reversed a decade-long trend in the opposite direction.
Safety and Efficacy of Transition from Inhaled Treprostinil to Parenteral Treprostinil in Selected Patients with Pulmonary Arterial Hypertension
Authors: Preston Ioana R. , Feldman Jeremy , White James , Franco Veronica , Ishizawar David , Burger Charles , Waxman Aaron B. , Hill Nicholas S. 
Published: August 2014

Guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend sequential add‐on therapy for patients who deteriorate or fail to improve clinically. However, it is not known whether these patients also benefit from transitioning from inhaled prostacyclins to parenteral prostacyclins. We sought to characterize PAH patients receiving inhaled treprostinil who were transitioned to parenteral treprostinil. We conducted a multicenter retrospective study at 7 PAH centers and collected reasons, methods, safety, and outcome of patients transitioned from inhaled treprostinil to parenteral treprostinil. Twenty‐six patients with pulmonary hypertension in group 1, 4, or 5 transitioned from inhaled treprostinil to parenteral treprostinil (10 intravenous, 16 subcutaneous). Twenty‐four patients were also on one or two oral therapies. Reasons for transition were clinical deterioration, lack of clinical improvement, and pregnancy (19, 6, and 1 patients, respectively). Transitions occurred in hospital, clinic, or home (17, 7, and 2 patients, respectively). Parenteral infusion was started after the last inhaled treatment at maintenance dose (13 patients), after the inhaled therapy was downtitrated to 18 μg (6 patients), or with an overlap of inhaled downtitration with parenteral uptitration (7 patients). The transition was safe; side effects included symptoms of prostacyclin overdose. Patients were followed for 3–18 months. At 3 months, 8 patients improved, 17 maintained their functional class, and 1 continued to deteriorate. In conclusion, selected PAH patients can be safely transitioned from inhaled treprostinil to parenteral treprostinil using a variety of methodologies in different settings with the expectation that patients will improve or at least remain clinically stable.
Denominator vectors and compatibility degrees in cluster algebras of finite type
Authors: Ceballos Cesar , Pilaud Vincent 
Published: August 2014

We present two simple descriptions of the denominator vectors of the cluster variables of a cluster algebra of finite type, with respect to any initial cluster seed: one in terms of the compatibility degrees between almost positive roots defined by S. Fomin and A. Zelevinsky, and the other in terms of the root function of a certain subword complex. These descriptions only rely on linear algebra. They provide two simple proofs of the known fact that the

d
d

-vector of any non-initial cluster variable with respect to any initial cluster seed has non-negative entries and is different from zero.
Eukaryotic translation initiation factor eIF5 promotes the accuracy of start codon recognition by regulating Pi release and conformational transitions of the preinitiation complex
Authors: Saini Adesh K , Nanda Jagpreet S , Martin-Marcos Pilar , Dong Jinsheng , Zhang Fan , Bhardwaj Monika , Lorsch Jon R , Hinnebusch Alan G 
Published: August 2014

AbstracteIF5 is the GTPase activating protein (GAP) for the eIF2·GTP·Met-tRNAiMet ternary complex with a critical role in initiation codon selection. Previous work suggested that the eIF5 mutation G31R/SUI5 elevates initiation at UUG codons by increasing GAP function. Subsequent work implicated eIF5 in rearrangement of the preinitiation complex (PIC) from an open, scanning conformation to a closed state at AUG codons, from which Pi is released from eIF2·GDP·Pi. To identify eIF5 functions crucial for accurate initiation, we investigated the consequences of G31R on GTP hydrolysis and Pi release, and the effects of intragenic G31R suppressors on these reactions, and on the partitioning of PICs between open and closed states. eIF5-G31R altered regulation of Pi release, accelerating it at UUG while decreasing it at AUG codons, consistent with its ability to stabilize the closed complex at UUG. Suppressor G62S mitigates both defects of G31R, accounting for its efficient suppression of UUG initiation in G31R,G62S cells; however suppressor M18V impairs GTP hydrolysis with little effect on PIC conformation. The strong defect in GTP hydrolysis conferred by M18V likely explains its broad suppression of Sui− mutations in numerous factors. We conclude that both of eIF5's functions, regulating Pi release and stabilizing the closed PIC conformation, contribute to stringent AUG selection invivo.
Rrd1p, an RNA polymerase II-specific prolyl isomerase and activator of phosphoprotein phosphatase, promotes transcription independently of rapamycin response
Authors: Sen Rwik , Malik Shivani , Frankland-Searby Sarah , Uprety Bhawana , Lahudkar Shweta , Bhaumik Sukesh R. 
Published: August 2014

AbstractRrd1p (resistance to rapamycin deletion 1) has been previously implicated in controlling transcription of rapamycin-regulated genes in response to rapamycin treatment. Intriguingly, we show here that Rrd1p associates with the coding sequence of a galactose-inducible and rapamycin non-responsive GAL1 gene, and promotes the association of RNA polymerase II with GAL1 in the absence of rapamycin treatment following transcriptional induction. Consistently, nucleosomal disassembly at GAL1 is impaired in the absence of Rrd1p, and GAL1 transcription is reduced in the Δrrd1 strain. Likewise, Rrd1p associates with the coding sequences of other rapamycin non-responsive and inducible GAL genes to promote their transcription in the absence of rapamycin treatment. Similarly, inducible, but rapamycin-responsive, non-GAL genes such as CTT1, STL1 and CUP1 are also regulated by Rrd1p. However, transcription of these inducible GAL and non-GAL genes is not altered in the absence of Rrd1p when the steady-state is reached after long transcriptional induction. Consistently, transcription of the constitutively active genes is not changed in the Δrrd1 strain. Taken together, our results demonstrate a new function of Rrd1p in stimulation of initial rounds of transcription, but not steady-state/constitutive transcription, of both rapamycin-responsive and non-responsive genes independently of rapamycin treatment.
Child-related characteristics predicting subsequent health-related quality of life in 8- to 14-year-old children with and without cerebellar tumors: a prospective longitudinal study
Authors: Bull Kim S. , Liossi Christina , Culliford David , Peacock Janet L. , Kennedy Colin R. ,   on behalf of the Children's Cancer and Leukaemia Group (CCLG)
Published: August 2014

AbstractBackgroundWe identified child-related determinants of health-related quality of life (HRQoL) in children aged 8–14 years who were treated for 2 common types of pediatric brain tumors.MethodsQuestionnaire measures of HRQoL and psychometric assessments were completed by 110 children on 3 occasions over 24 months. Of these 110, 72 were within 3 years of diagnosis of a cerebellar tumor (37 standard-risk medulloblastoma, 35 low-grade cerebellar astrocytoma), and 38 were in a nontumor group. HRQoL, executive function, health status, and behavioral difficulties were also assessed by parents and teachers as appropriate. Regression modeling was used to relate HRQoL z scores to age, sex, socioeconomic status, and 5 domains of functioning: Cognition, Emotion, Social, Motor and Sensory, and Behavior.ResultsHRQoL z scores were significantly lower after astrocytoma than those in the nontumor group and significantly lower again in the medulloblastoma group, both by self-report and by parent-report. In regression modeling, significant child-related predictors of poorer HRQoL z scores by self-report were poorer cognitive and emotional function (both z scores) and greater age (years) at enrollment (B = 0.038, 0.098, 0.136, respectively). By parent-report, poorer cognitive, emotional and motor or sensory function (z score) were predictive of lower subsequent HRQoL of the child (B = 0.043, 0.112, 0.019, respectively), while age at enrollment was not.ConclusionsEarly screening of cognitive and emotional function in this age group, which are potentially amenable to change, could identify those at risk of poor HRQoL and provide a rational basis for interventions to improve HRQoL.
Standardized Electrolyte Supplementation and Fluid Management Improves Survival During Amphotericin Therapy for Cryptococcal Meningitis in Resource-Limited Settings
Authors: Bahr Nathan C. , Rolfes Melissa A. , Musubire Abdu , Nabeta Henry , Williams Darlisha A. , Rhein Joshua , Kambugu Andrew , Meya David B. , Boulware David R. 
Published: August 2014

Abstract
Background.  Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokalemia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa.
Methods.  Human immunodeficiency virus-infected, antiretroviral therapy naive adults with cryptococcal meningitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphotericin B deoxycholate induction treatment. Intravenous fluid use was intermittent in 2001–2002, and universal in 2006–2012. In 2001–2009, serum potassium (K+) was monitored on days 1, 7, and 14 of treatment with replacement (K+, Mg2+) per clinician discretion. In 2011–2012, K+ was measured on days 1, 5, and approximately every 48 hours thereafter with universal electrolyte (K+, Mg2+) supplementation and standardized replacement. Clinical outcomes were retrospectively compared between fluid and electrolyte management strategies.
Results.  With limited intravenous fluids, the 14-day survival was 49% in 2001–2002. With universal intravenous fluids, the 30-day survival improved to 62% in 2006–2010 (P = .003). In 2011–2012, with universal supplementation of fluids and electrolytes, 30-day cumulative survival improved to 78% (P = .021 vs 2006–2010 cohort). The cumulative incidence of severe hypokalemia (&lt;2.5 mEq/L) decreased from 38% in 2010 to 8.5% in 2011–2012 with universal supplementation (P &lt; .001).
Conclusions.  Improved survival was seen in a resource-limited setting with proactive fluid and electrolyte management (K+, Mg2+), as part of comprehensive amphotericin-based cryptococcal therapy.