bluuebunny/crossref_metadata_2025 huggingface dataset:
2039
Authors: Bress Adam , Colantonio Lisandro D. , Booth John N. , Spruill Tanya M. , Ravenell Joseph , Butler Mark , Shallcross Amanda J. , Seals Samantha R. , Reynolds Kristi , Ogedegbe Gbenga , Shimbo Daichi , Muntner Paul
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Clinical guidelines recommend using predicted atherosclerotic cardiovascular disease (ASCVD) risk to inform treatment decisions. The objective was to compare the contribution of changes in modifiable risk factors Versus aging to the development of high 10-year predicted ASCVD risk. METHODS/STUDY POPULATION: Prospective follow-up of the Jackson Heart Study, an exclusively African-American cohort, at visit 1 (2000–2004) and visit 3 (2009–2012). Analyses included 1115 African-American participants without a high 10-year predicted ASCVD risk (<7.5%), hypertension, diabetes, or ASCVD at visit 1. We used the Pooled Cohort equations to calculate the incidence of high (≥7.5%) 10-year predicted ASCVD risk at visit 3. We recalculated the percentage with a high 10-year predicted ASCVD risk at visit 3 assuming each risk factor [age, systolic blood pressure (SBP), antihypertensive medication use, diabetes, smoking, total and high-density lipoprotein cholesterol], one at a time, did not change from visit 1. RESULTS/ANTICIPATED RESULTS: The mean age at visit 1 was 45.2±9.5 years. Overall, 30.9% (95% CI 28.3%–33.4%) of participants developed high 10-year predicted ASCVD risk. Aging accounted for 59.7% (95% CI 54.2%–65.1%) of the development of high 10-year predicted ASCVD risk compared with 32.8% (95% CI 27.0%–38.2%) for increases in SBP or antihypertensive medication initiation and 12.8% (95% CI 9.6%–16.5%) for incident diabetes. Among participants <50 years, the contribution of increases in SBP or antihypertensive medication initiation was similar to aging. DISCUSSION/SIGNIFICANCE OF IMPACT: Increases in SBP and antihypertensive medication initiation are major contributors to the development of high 10-year predicted ASCVD risk in African Americans, particularly among younger adults.
2187
Authors: Valentine-King Marissa , Brown Mary B.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Urinary tract infections (UTIs) serve as one of the most common infections affecting women. With rising reports of antibiotic resistance (ABR), which can prolong illness and limit treatment options, the Infectious Disease Society of America recommends using local resistance patterns to shape empirical treatment selection. Although no studies have evaluated ABR in Ureaplasma spp. urinary isolates in college-aged women, regional studies in the Southeast United States have found levels of tetracycline resistance in over 30% of Ureaplasma spp. clinical isolates. Thus, this study aims to determine the antibiogram for 73 Ureaplasma spp. and 10 Mycoplasma hominis isolates collected from women with first-time UTI against a panel of 9 antibiotics, and assess resistant isolates for genetic mechanisms associated with resistance. METHODS/STUDY POPULATION: This study used archival samples and data collected from college-aged women with first-time UTI recruited to participate in a prospective cohort study conducted at a student healthcare facility from 2001 to 2006 in Florida. Ureaplasma spp. and M. hominis isolates cultured from urine samples collected at the initial clinical presentation and for any recurrent UTI were evaluated for susceptibility to a panel of 9 antibiotics (8 for M. hominis) using validated microbroth and agar dilution methods, respectively. Ureaplasma spp. isolates were tested against azithromycin, chloramphenicol, ciprofloxacin, clindamycin, erythromycin, doxycycline, gentamicin, levofloxacin, and tetracycline. M. hominis isolates underwent the same testing, with the addition of linezolid and exclusion of azithromycin and erythromycin, as M. hominis is intrinsically resistance to 14 and 15-membered macrolides and azilides. PCR and Sanger sequencing were employed to identify molecular mechanisms associated with resistance. RESULTS/ANTICIPATED RESULTS: Of the 73 Ureaplasma spp. isolates, 1 isolate was resistant to levofloxacin (MIC: 4 µg/mL) and 1 to tetracycline (MIC: 8 µg/mL). All M. hominis isolates were sensitive. For the Ureaplasma spp. isolates, MIC90s were highest against gentamicin (32 µg/mL) and lowest against doxycycline (0.25 µg/mL). PCR amplification identified tetM present in the tetracycline resistant isolate, an established gene associated with tetracycline resistance in Ureaplasma spp. A S83W mutation within the quinolone-resistance-determining region (QRDR) of parC was detected in the levofloxacin resistant isolate. DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, antibiotic resistance in this population of college-aged women with first-time UTI was low. A previous study detected a novel S83W substitution in a perinatal Ureaplasma spp. isolate from Japan, and provided in silico evidence that a S83W change would prevent levofloxacin from binding to its target. However, that study was unable to cultivate the isolate. Our study has provided the corresponding phenotypic evidence that a S83W substitution results in quinolone resistance in Ureaplasma spp.
2220
Authors: Melin Kyle , Duconge Jorge , Hernandez Suarez Dagmar F.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to measure the association of CYP2C19 (*1-*8,*17), ABCB1(C3435T; rs1045642), PON1 (p.Q192R; rs662), and B4GALT2 (c.909 C>T and c.366 G>C) gene polymorphisms in the Caribbean Hispanic population with major adverse cardiovascular events (MACE). METHODS/STUDY POPULATION: Patients of Caribbean Hispanic ethnicity from all geographic regions of the Island of Puerto Rico, male and female, aged >21 will be recruited. Cases will consist of patients receiving a daily clopidogrel dose of 75 mg following acute coronary syndrome (ACS) who experience a MACE within the first year of treatment. Control study patients must have received clopidogrel 75 mg daily for a minimum of 1 year without experiencing MACE. Genomic DNA samples will be genotyped to determine the frequency distribution of major CYP2C19, ABCB1, PON1, and B4GALT2 gene polymorphisms. Observed frequencies will be compared with other reported populations. An association study will be performed between genetic variables and MACE and a multivariable logistic regression model (additive) will be constructed. RESULTS/ANTICIPATED RESULTS: We anticipate finding a significant association between major genetic determinants of clopidogrel response and MACE where cases with MACE will carry higher frequency of CYP2C19, ABCB1, PON1, and B4GALT2. DISCUSSION/SIGNIFICANCE OF IMPACT: As the range of multiloci allelic combinations in admixed Caribbean Hispanics is higher than in other populations due to its unique 500-year history of genomic admixture, a wide spectrum of genetic variances is expected to be present in the study population. Determining the prevalence and effect of CYP2C19, ABCB1, PON1, and B4GALT2 polymorphisms holds the potential to personalize anti-platelet treatment for Caribbean Hispanic patients requiring treatment after ACS.
Assessing a National Collaborative Program To Prevent Catheter-Associated Urinary Tract Infection in a Veterans Health Administration Nursing Home Cohort
Authors: Krein Sarah L. , Greene M. Todd , King Beth , Welsh Deborah , Fowler Karen E. , Trautner Barbara W. , Ratz David , Saint Sanjay , Roselle Gary , Clifton Marla , Kralovic Stephen M. , Martin Tina , Mody Lona
Published: May 2018

OBJECTIVE

Collaborative programs have helped reduce catheter-associated urinary tract infection (CAUTI) rates in community-based nursing homes. We assessed whether collaborative participation produced similar benefits among Veterans Health Administration (VHA) nursing homes, which are part of an integrated system.

SETTING

This study included 63 VHA nursing homes enrolled in the “AHRQ Safety Program for Long-Term Care,” which focused on practices to reduce CAUTI.

METHODS

Changes in CAUTI rates, catheter utilization, and urine culture orders were assessed from June 2015 through May 2016. Multilevel mixed-effects negative binomial regression was used to derive incidence rate ratios (IRRs) representing changes over the 12-month program period.

RESULTS

There was no significant change in CAUTI among VHA sites, with a CAUTI rate of 2.26 per 1,000 catheter days at month 1 and a rate of 3.19 at month 12 (incidence rate ratio [IRR], 0.99; 95% confidence interval [CI], 0.67–1.44). Results were similar for catheter utilization rates, which were 11.02% at month 1 and 11.30% at month 12 (IRR, 1.02; 95% CI, 0.95–1.09). The numbers of urine cultures per 1,000 residents were 5.27 in month 1 and 5.31 in month 12 (IRR, 0.93; 95% CI, 0.82–1.05).

CONCLUSIONS

No changes in CAUTI rates, catheter use, or urine culture orders were found during the program period. One potential reason was the relatively low baseline CAUTI rate, as compared with a cohort of community-based nursing homes. This low baseline rate is likely related to the VHA’s prior CAUTI prevention efforts. While broad-scale collaborative approaches may be effective in some settings, targeting higher-prevalence safety issues may be warranted at sites already engaged in extensive infection prevention efforts.

Infect Control Hosp Epidemiol 2018;820–825
Characterization of three heat shock protein 70 genes fromLiriomyza trifoliiand expression during thermal stress and insect development
Authors: Chang Y.-W. , Zhang X.-X. , Chen J.-Y. , Lu M.-X. , Gong W.-R. , Du Y.-Z.
Published: May 2018

Heat shock proteins (HSPs) participate in diverse physiological processes in insects, and HSP70 is one of the most highly conserved proteins in the HSP family. In this study, full-length cDNAs of three HSP70 genes (Lthsc70,Lthsp701, andLthsp702) were cloned and characterized fromLiriomyza trifolii, an important invasive pest of vegetable crops and horticultural crops worldwide. These three HSP70s exhibited signature sequences and motifs that are typical of the HSP70 family. The expression patterns of the threeLthsp70s during temperature stress and in different insect development stages were studied by real-time quantitative PCR.Lthsp701was strongly induced by high- and low-temperature stress, butLthsc70andLthsp702were not very sensitive to temperature changes. All threeLthsp70s were expressed during insect development stages, but the expression patterns were quite different. The expression ofLthsc70andLthsp702showed significant differences in expression during leafminer development;Lthsc70was most highly expressed in female adults, whereasLthsp702was abundantly expressed in larvae and prepupae.Lthsp701expression was not significantly different among leafminer stages. These results suggest that functional differentiation within theLtHSP70 subfamily has occurred in response to thermal stress and insect development.
The tectonometamorphic evolution of the Uppermost Unit south of the Dikti Mountains, Crete
Authors: MARTHA SILVIU O. , ZULAUF GERNOLD , DÖRR WOLFGANG , BINCK JANNES J. , NOWARA PATRICK M. , XYPOLIAS PARASKEVAS
Published: May 2018

We present a new geological map and new structural, petrographical and geochronological data from the Uppermost Unit of the Cretan nappe pile exposed south of the Dikti Mountains in eastern Crete (Greece). Based on these data, the Uppermost Unit in the study area can be subdivided (from bottom to top) into the Arvi Unit, Theodorii Greenschist and Asterousia Crystalline Complex (ACC)-type rocks. The ACC-type rocks have been affected by polyphase deformation (D1–D3) and metamorphism. Relics of the D1phase are preserved as internal foliation in garnet porphyroblasts. D2top-to-the SE shearing under upper amphibolite facies conditions led to the dominant foliation. After post-D2exhumation, parts of the ACC-type rocks were affected by contact metamorphism of a non-exposed pluton, which intruded at a depth below 10 km during Campanian time (74±2Ma; laser ablation inductively coupled plasma mass spectrometry on zircon). This age, obtained from zircon of chiastolite hornfels, is in line with intrusion ages of ACC-type (meta)granitoids exposed on Crete and on Anafi. The S2-foliation of the ACC-type rocks was reactivated during the late phase of contact metamorphism by D3top-to-the SE shearing. Latest Cretaceous cross-mica with low silicon content post-dates this shearing event. During middle Paleocene time, the ACC was thrust on top of the Theodorii Greenschist. This thrusting event as well as subsequent brittle thrusting of the greenschists and the ACC-type rocks on top of the prehnite-pumpellyite facies metamorphic Arvi Unit was still accommodated by top-to-the SE kinematics, which is the dominant kinematics of the Uppermost Unit on Crete and on Anafi.
Introduction
Authors: El-Mahdi Rabab , Lust Ellen
Published: May 2018

The nation-state is in crisis. The increasing mobility of capital and information, unprecedented waves of people moving across borders, and rise of actors, such as ISIS, unwilling to abide by the rules of the Westphalian system, challenge the very notion of territoriality, citizenship, sovereignty, and the state's monopoly over the legitimate use of force. Studies on the Middle East and North Africa since the Arab uprisings took the region by storm, upending “conventional wisdom” held by many political scientists and scholars, have focused largely on the causes, genealogy, and procedural outcomes of the events. These are important, but as we shall see, the uprisings also highlighted the need to think carefully about how the modern state has changed, is being adapted, or has been superseded. How is the “state,” a foundational conceptual construct in the social sciences, to be located in light of these events? And to what extent do the concepts we employ and the language we use accurately reflect and allow us to interrogate realities, or do they obscure them? This roundtable aims to spark this much-needed discussion.
A window beneath the skin: how computed tomography assessment of body composition can assist in the identification of hidden wasting conditions in oncology that profoundly impact outcomes
Authors: Daly L. E. , Prado C. M. , Ryan A. M.
Published: May 2018

Advancements in image-based technologies and body composition research over the past decade has led to increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation (MA), as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities can be highly prevalent in patients with cancer (ranging between 10 and 90 %), depending on the cohort under investigation and diagnostic criteria used. Importantly, both low muscle mass and low MA have been associated with poorer tolerance to chemotherapy, increased risk of post-operative infectious and non-infectious complications, increased length of hospital stay and poorer survival in patients with cancer. Studies have shown that systemic antineoplastic treatment can exacerbate losses in muscle mass and MA, with reported loss of skeletal muscle between 3 and 5 % per 100 d, which are increased exponentially with progressive disease and proximity to death. At present, no effective medical intervention to improve muscle mass and MA exists. Most research to date has focused on treating muscle depletion as part of the cachexia syndrome using nutritional, exercise and pharmacological interventions; however, these single-agent therapies have not provided promising results. Rehabilitation care to modify body composition, either increasing muscle mass and/or MA should be conducted, and its respective impact on oncology outcomes explored. Although the optimal timing and treatment strategy for preventing or delaying the development of muscle abnormalities are yet to be determined, multimodal interventions initiated early in the disease trajectory appear to hold the most promise.
The integral isomorphism behind row removal phenomena for schur algebras
Authors: BOWMAN CHRISTOPHER , GIANNELLI EUGENIO
Published: May 2018

We explain and generalise row and column removal phenomena for Schur algebras via integral isomorphisms between subquotients of these algebras. In particular, we prove new reduction formulae for p-Kostka numbers.
The Law of Negligence as Reported in The Times, 1785–1820
Authors: Oldham James
Published: May 2018

Historically, the clear recognition by the courts that all adults in public intercourse owe a duty of reasonable care to avoid injuring others has been seen as an early nineteenth century development. Occasionally it is recognized that what is known about the emergence of the tort of negligence in English law comes almost entirely from the printed reports of civil (plea side) cases tried in the three common law courts (King's Bench, Common Pleas, and Exchequer). It was not until the 1790s that regular printed reports of jury trials (or nisi prius cases, as they were called) began, and even then, enlightenment from the nisi prius reports was limited. Most of those reports were sketchy, and very few included instructions given to the jury by the trial judge. More importantly, the reports covered only a small fraction of the jury trials that were conducted by the common law courts. The overwhelming majority of civil jury trials ended with the jury verdict (or an occasional nonsuit), with no post-trial proceedings, and what happened in many thousands of these plea-side jury trials in the late eighteenth and early nineteenth centuries has been something of a black hole in the historical record.
On the Persistent Shape and Coherence of Pulsating Auroral Patches
Authors: Humberset B. K. , Gjerloev J. W. , Mann I. R. , Michell R. G. , Samara M.
Published: May 2018

The pulsating aurora covers a broad range of fluctuating shapes that are poorly characterized. The purpose of this paper is therefore to provide objective and quantitative measures of the extent to which pulsating auroral patches maintain their shape, drift and fluctuate in a coherent fashion. We present results from a careful analysis of pulsating auroral patches using all‐sky cameras. We have identified four well‐defined individual patches that we follow in the patch frame of reference. In this way we avoid the space‐time ambiguity which complicates rocket and satellite measurements. We find that the shape of the patches is remarkably persistent with 85–100% of the patch being repeated for 4.5–8.5 min. Each of the three largest patches has a temporal correlation with a negative dependence on distance, and thus does not fluctuate in a coherent fashion. A time‐delayed response within the patches indicates that the so‐called streaming mode might explain the incoherency. The patches appear to drift differently from the SuperDARN‐determined
convection velocity. However, in a nonrotating reference frame the patches drift with 230–287 m/s in a north eastward direction, which is what typically could be expected for the convection return flow.
Comparison of Cloudy‐Sky Downward Longwave Radiation Algorithms Using Synthetic Data, Ground‐Based Data, and Satellite Data
Authors: Yu Shanshan , Xin Xiaozhou , Liu Qinhuo , Zhang Hailong , Li Li
Published: May 2018

Cloud plays a crucial role in surface downward longwave radiation (DLR). To determine optimal algorithms for cloud‐sky DLR calculation under various climates, three types of algorithms were assessed, (i) four empirical algorithms determining cloudy DLR by simple cloud correction using the cloud fraction, (ii) three parameterized algorithms determining the cloud contribution by cloud temperature, and (iii) a semiempirical algorithm, Zhou‐Cess, parameterized by the cloud water path. A sensitivity study was conducted using a Moderate Resolution Transmittance (MODTRAN) code to first determine the sensitive cloud parameters of DLR. Then, these algorithms were validated using synthetic data simulated by MODTRAN, ground‐observed data, and satellite‐observed data. When all the input parameters were accurate, the cloud‐correction algorithms showed poor performance. Cloud‐temperature‐based algorithms showed much better results but exhibited positive systematic biases. The Zhou‐Cess algorithm performed best but could not precisely describe the effect caused by cloud variations. When these algorithms were applied to ground‐ and satellite‐based data, the accuracies of DLR calculations were affected by the uncertainty in the atmospheric and cloud parameters. The simple empirical algorithms showed the poorest results. The cloud‐temperature‐based algorithms were greatly influenced by the uncertainty in cloud base temperature and cloud fraction and showed acceptable results when cloud fractions were accurate. The Zhou‐Cess algorithm revealed the best results at most sites and was less impacted by cloud parameter uncertainties; therefore, this algorithm is suggested for cloudy‐sky DLR calculation with poor‐quality cloud parameters.
A New Hybrid Coupled Model of Atmosphere, Ocean Physics, and Ocean Biogeochemistry to Represent Biogeophysical Feedback Effects in the Tropical Pacific
Authors: Zhang Rong‐Hua , Tian Feng , Wang Xiujun
Published: May 2018

Multiple processes are involved in modulating the El Niño‐Southern Oscillation (ENSO) in the tropical Pacific, and these processes are neither well‐represented nor well‐understood in climate models. A new hybrid coupled model (HCM) of atmosphere, ocean physics, and ocean biogeochemistry (AOPB) is developed to represent the feedback from ocean biogeochemistry onto ocean physics via modulating the penetration of shortwave radiation in the upper ocean. An ocean biogeochemistry model is coupled with a simplified ocean‐atmosphere system consisting of an ocean general circulation model (OGCM) and a statistical atmospheric model for interannual anomalies of wind stress (τ). The HCM AOPB serves as a simple Earth system for the tropical Pacific to represent the coupling among the atmospheric and physical and biogeochemical ocean components. Model experiments are performed to illustrate this new model's ability to depict the mean ocean state and interannual variability associated with the ENSO. The relationships among anomaly fields are analyzed to illustrate the ocean biogeochemistry‐induced heating feedback and its modulating effects on the ENSO, which is characterized by a negative feedback. The underlying processes and mechanisms are analyzed and can be attributed to dominant modulation of the penetrative solar radiation through the base of the mixed layer (ML). It is demonstrated that the ocean biogeochemistry‐induced negative feedback is mainly driven by more solar radiation penetrating out of the ML during El Nino and less penetrating during La Nina. Further model applications to studies on these processes and biogeochemical‐physical interactions are discussed.
New Insights into Continental Deformation in Northwestern Tibet
Authors: Cook Terri
Published: May 2018

A new surface velocity map shows strain localized along major strike-slip features, suggesting the central Tibetan Plateau is not deforming as a fluid in response to gravitational collapse.
NSF and Air Force Plan to Better Coordinate Research Projects
Authors: Showstack Randy
Published: May 2018

A newly released letter of intent sets up a new partnership that could benefit both agencies. Initial focus areas for consideration include space operations and geosciences.
Solar Wind and Seasonal Influence on Ionospheric Currents From Swarm and CHAMP Measurements
Authors: Laundal K. M. , Finlay C. C. , Olsen N. , Reistad J. P.
Published: May 2018

We present a new climatological model of the ionospheric current system, determined from magnetic measurements taken by the Challenging Minisatellite Payload (CHAMP) and Swarm satellites. The model describes the horizontal currents in the ionosphere, below the satellites, and the field‐aligned (Birkeland) currents that connect the ionosphere with the magnetosphere. The model provides ionospheric current values at any location as continuous functions of solar wind speed, interplanetary magnetic field, dipole tilt angle, and the F10.7 index of solar flux. Geometric distortions due to variations in the Earth's main magnetic field are taken into account, thus allowing for precise comparisons between the two hemispheres. The model is the first of its kind to describe the full 3‐D electric currents and not only the field‐aligned or the equivalent horizontal current. We use this capability to demonstrate a key difference between seasons: During winter, the total horizontal current is almost entirely confined to the auroral oval, for all interplanetary magnetic field orientations, where it connects upward and downward Birkeland currents. During more sunlit conditions, the horizontal current extends beyond the auroral oval and is a sum of currents connecting Birkeland currents and currents that circulate in the ionosphere. The westward electrojet is the only large‐scale current structure that is persistent across seasons. Comparison with average convection maps suggests that it is comprised largely of Hall currents, which connect to Birkeland currents in the winter but not in summer.
Sustained Uplift at a Continental Rift Caldera
Authors: Lloyd Ryan , Biggs Juliet , Birhanu Yelebe , Wilks Matthew , Gottsmann Joachim , Kendall J.‐Michael , Ayele Atalay , Lewi Elias , Eysteinsson Hjálmar
Published: May 2018

Caldera systems are often restless and experience pulses of uplift and subsidence, with a weak, but significant link to eruption. Characterizing the spatial and temporal patterns of deformation episodes provides insight into the processes responsible for unrest and the architecture of magmatic and hydrothermal systems. Here we combine interferometric synthetic aperture radar images with data from Global Positioning System and a network of seismometers at a continental rift caldera Corbetti, Ethiopia. We document inflation that started mid‐2009 and is ongoing as of 2017, with associated seismicity. We investigate the temporal evolution of the deformation source using a Hastings‐Metropolis algorithm to estimate posterior probability density functions for source model parameters and use the Akaike information criterion to inform model selection. Testing rectangular dislocation and point sources, we find a point source at a depth of 6.6 km (95% confidence: 6.3 − 6.8 km) provides the statistically justified fit. The location of this source is coincident with a conductive anomaly derived from magnetotelluric measurements. We use a joint inversion of two geodetic data sets to produce a time series, which shows a volume input of 1.0 × 107 m3/year. This is the first observation of a prolonged period of magma reservoir growth in the Main Ethiopian Rift and has implications for hazard assessment and monitoring. Corbetti is < 20 km from two major population centers and has estimated return periods of ∼500 and ∼900 years for lava flows and Plinian eruptions, respectively. Our results highlight the need for long‐term geodetic monitoring and the application of statistically robust methods to characterize deformation sources.
PILAR: A Model of Collaboration to Encapsulate Social Psychology
Authors: Heslop Benjamin , Stojanovski Elizabeth , Paul Jonathan , Bailey Kylie
Published: May 2018

This article presents an iterative examination of a grounded theory of collaboration in conjunction with social psychology literature. The resulting PILAR (Prospects, Involved, Liked, Agency, Respect) model of collaboration encapsulates over 30 social and group psychology (SGP) theories, including social identity theory, social network analysis, and psychological safety. Selected works of the early 20th-century scholars Lewin, Moreno, Simmel, and Foucault resonate with the PILAR model. We considered that, in constructing a generalized model of collaboration made possible by the availability of modern SGP theory, PILAR may represent advancement toward accomplishing these early scholars’ original intent. To validate PILAR, we proposed an empirical investigation for its consistency with organizational psychology, positive psychology, and appreciative inquiry, and for testing whether learning PILAR may improve collaboration skills for individuals lacking empathy.
Hepatic steatosis associated with decreased β-oxidation and mitochondrial function contributes to cell damage in obese mice after thermal injury
Authors: Diao Li , Auger Christopher , Konoeda Hisato , Sadri Ali-Reza , Amini-Nik Saeid , Jeschke Marc G.
Published: May 2018

Severely burned patients who are morbidly obese have poor clinical outcomes with aggravated metabolic consequences, a higher incidence of multiple organ dysfunction/failure, and significantly increased morbidity and mortality. The underlying mechanisms of these adverse outcomes are essentially unknown. Since the liver is one of the central metabolic organs, we hypothesized that thermal injury in obese patients leads to substantially increased lipolysis, hepatic fat infiltration, resulting in profound hepatic cellular and organellar alterations, consequently causing liver damage and severely augmented metabolic dysfunction. We tested this hypothesis using an obese mouse model subjected to a 20% total body surface area burn injury. C57BL/6 mice were randomly divided into low-fat diet (LFD) and high-fat diet (HFD) sham and burn groups (n = 6 per group) and fed for 16 weeks. 7 days after the thermal injury portal and cardiac blood were taken separately and liver tissue was collected for western blotting and immunohistochemical analysis. Gross examination of the liver showed apparent lipid infiltration in HFD fed and burned mice. We confirmed that augmented ER stress and inhibition of Akt-mTOR signaling dysregulated calcium homeostasis, contributed to the decrease of ER–mitochondria contact, and reduced mitochondrial β-oxidation in HFD fed and burned mice, leading to profound hepatic fat infiltration and substantial liver damage, hence increased morbidity and mortality. We conclude that obesity contributes to hepatic fat infiltration by suppressing β-oxidation, inducing cell damage and subsequent organ dysfunction after injury.
Autophagy diminishes the early interferon-β response to influenza A virus resulting in differential expression of interferon-stimulated genes
Authors: Perot Brieuc P. , Boussier Jeremy , Yatim Nader , Rossman Jeremy S. , Ingersoll Molly A. , Albert Matthew L.
Published: May 2018

Influenza A virus (IAV) infection perturbs metabolic pathways such as autophagy, a stress-induced catabolic pathway that crosstalks with cellular inflammatory responses. However, the impact of autophagy perturbation on IAV gene expression or host cell responses remains disputed. Discrepant results may be a reflection of in vivo studies using cell-specific autophagy-related (Atg) gene-deficient mouse strains, which do not delineate modification of developmental programmes from more proximal effects on inflammatory response. In vitro experiments can be confounded by gene expression divergence in wild-type cultivated cell lines, as compared to those experiencing long-term absence of autophagy. With the goal to investigate cellular processes within cells that are competent or incompetent for autophagy, we generated a novel experimental cell line in which autophagy can be restored by ATG5 protein stabilization in an otherwise Atg5-deficient background. We confirmed that IAV induced autophagosome formation and p62 accumulation in infected cells and demonstrated that perturbation of autophagy did not impact viral infection or replication in ATG5-stablized cells. Notably, the induction of interferon-stimulated genes (ISGs) by IAV was diminished when cells were autophagy competent. We further demonstrated that, in the absence of ATG5, IAV-induced interferon-β (IFN-β) expression was increased as compared to levels in autophagy-competent lines, a mechanism that was independent of IAV non-structural protein 1. In sum, we report that induction of autophagy by IAV infection reduces ISG expression in infected cells by limiting IFN-β expression, which may benefit viral replication and spread.
Natural compound Oblongifolin C confers gemcitabine resistance in pancreatic cancer by downregulating Src/MAPK/ERK pathways
Authors: Li Yang , Xi Zhichao , Chen Xiaoqiong , Cai Shuangfan , Liang Chen , Wang Zhen , Li Yingyi , Tan Hongsheng , Lao Yuanzhi , Xu Hongxi
Published: May 2018

Gemcitabine (GEM)-induced drug resistance is the major reason for the failure of chemotherapy in pancreatic cancer (PC). In this study, we found that Oblongifolin C (OC) efficiently inhibited PC cell proliferation by inducing G0/G1 arrest and apoptosis. Also, our mechanism study demonstrated that OC re-sensitized the GEM-resistant PC cells through the ubiquitin-proteasome-dependent degradation of Src, and then downregulating the MAPK pathway. Knockdown of Src plus OC resulted in a greater inhibitory effect in GEM-resistant PC cells. In contrast, Src overexpression reversed OC-mediated chemosensitization, thereby implicating Src in the action of OC. Moreover, our in vivo study showed that OC suppressed the tumor growth via the downregulation of Src, and enhanced the chemosensitivity of GEM-resistant PC to GEM. Overall, our results have revealed that OC is applicable as a promising agent for overcoming GEM-resistant PC, especially with aberrant Src expression.
Downregulation of the psychiatric susceptibility gene Cacna1c promotes mitochondrial resilience to oxidative stress in neuronal cells
Authors: Michels Susanne , Ganjam Goutham K. , Martins Helena , Schratt Gerhard M. , Wöhr Markus , Schwarting Rainer K. W. , Culmsee Carsten
Published: May 2018

Affective disorders such as major depression and bipolar disorder are among the most prevalent forms of mental illness and their etiologies involve complex interactions between genetic and environmental risk factors. Over the past ten years, several genome wide association studies (GWAS) have identified CACNA1C as one of the strongest genetic risk factors for the development of affective disorders. However, its role in disease pathogenesis is still largely unknown. Vulnerability to affective disorders also involves diverse environmental risk factors such as perinatal insults, childhood maltreatment, and other adverse pathophysiological or psychosocial life events. At the cellular level, such environmental influences may activate oxidative stress pathways, thereby altering neuronal plasticity and function. Mitochondria are the key organelles of energy metabolism and, further, highly important for the adaptation to oxidative stress. Accordingly, multiple lines of evidence including post-mortem brain and neuro-imaging studies suggest that psychiatric disorders are accompanied by mitochondrial dysfunction. In this study, we investigated the effects of Cacna1c downregulation in combination with glutamate-induced oxidative stress on mitochondrial function, Ca2+ homeostasis, and cell viability in mouse hippocampal HT22 cells. We found that the siRNA-mediated knockdown of Cacna1c preserved mitochondrial morphology, mitochondrial membrane potential, and ATP levels after glutamate treatment. Further, Cacna1c silencing inhibited excessive mitochondrial reactive oxygen species formation and calcium influx, and protected the HT22 cells from oxidative cell death. Overall, our findings suggest that the GWAS-confirmed psychiatric risk gene CACNA1C plays a major role in oxidative stress pathways with particular impact on mitochondrial integrity and function.
Enantioselective reduction of sulfur-containing cyclic imines through biocatalysis
Authors: Zumbrägel Nadine , Merten Christian , Huber Stefan M. , Gröger Harald
Published: May 2018

The 3-thiazolidine ring represents an important structural motif in life sciences molecules. However, up to now reduction of 3-thiazolines as an attractive approach failed by means of nearly all chemical reduction technologies for imines. Thus, the development of an efficient general and enantioselective synthetic technology giving access to a range of such heterocycles remained a challenge. Here we present a method enabling the reduction of 3-thiazolines with high conversion and high to excellent enantioselectivity (at least 96% and up to 99% enantiomeric excess). This technology is based on the use of imine reductases as catalysts, has a broad substrate range, and is also applied successfully to other sulfur-containing heterocyclic imines such as 2H-1,4-benzothiazines. Moreover the effiency of this biocatalytic technology platform is demonstrated in an initial process development leading to 99% conversion and 99% enantiomeric excess at a substrate loading of 18 g/L in the presence of designer cells.
AID/APOBEC-like cytidine deaminases are ancient innate immune mediators in invertebrates
Authors: Liu Mei-Chen , Liao Wen-Yun , Buckley Katherine M. , Yang Shu Yuan , Rast Jonathan P. , Fugmann Sebastian D.
Published: May 2018

In the course of both innate and adaptive immunity, cytidine deaminases within the activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) family modulate immune responses by mutating specific nucleic acid sequences of hosts and pathogens. The evolutionary emergence of these mediators, however, seems to coincide precisely with the emergence of adaptive immunity in vertebrates. Here, we show a family of genes in species within two divergent invertebrate phyla—the echinoderm Strongylocentrotus purpuratus and the brachiopod Lingula anatina—that encode proteins with similarities in amino acid sequence and enzymatic activities to the vertebrate AID/APOBECs. The expression of these invertebrate factors is enriched in tissues undergoing constant, direct interactions with microbes and can be induced upon pathogen challenge. Our findings suggest that AID/APOBEC proteins, and their function in immunity, emerged far earlier than previously thought. Thus, cytidine deamination is probably an ancient innate immune mechanism that predates the protostome/deuterostome divergence.
Myosin1D is an evolutionarily conserved regulator of animal left–right asymmetry
Authors: Juan Thomas , Géminard Charles , Coutelis Jean-Baptiste , Cerezo Delphine , Polès Sophie , Noselli Stéphane , Fürthauer Maximilian
Published: May 2018

The establishment of left–right (LR) asymmetry is fundamental to animal development, but the identification of a unifying mechanism establishing laterality across different phyla has remained elusive. A cilia-driven, directional fluid flow is important for symmetry breaking in numerous vertebrates, including zebrafish. Alternatively, LR asymmetry can be established independently of cilia, notably through the intrinsic chirality of the acto-myosin cytoskeleton. Here, we show that Myosin1D (Myo1D), a previously identified regulator of Drosophila LR asymmetry, is essential for the formation and function of the zebrafish LR organizer (LRO), Kupffer’s vesicle (KV). Myo1D controls the orientation of LRO cilia and interacts functionally with the planar cell polarity (PCP) pathway component VanGogh-like2 (Vangl2), to shape a productive LRO flow. Our findings identify Myo1D as an evolutionarily conserved regulator of animal LR asymmetry, and show that functional interactions between Myo1D and PCP are central to the establishment of animal LR asymmetry.
Large-area plastic nanogap electronics enabled by adhesion lithography
Authors: Semple James , Georgiadou Dimitra G. , Wyatt-Moon Gwenhivir , Yoon Minho , Seitkhan Akmaral , Yengel Emre , Rossbauer Stephan , Bottacchi Francesca , McLachlan Martyn A. , Bradley Donal D. C. , Anthopoulos Thomas D.
Published: May 2018

Large-area manufacturing of flexible nanoscale electronics has long been sought by the printed electronics industry. However, the lack of a robust, reliable, high throughput and low-cost technique that is capable of delivering high-performance functional devices has hitherto hindered commercial exploitation. Herein we report on the extensive range of capabilities presented by adhesion lithography (a-Lith), an innovative patterning technique for the fabrication of coplanar nanogap electrodes with arbitrarily large aspect ratio. We use this technique to fabricate a plethora of nanoscale electronic devices based on symmetric and asymmetric coplanar electrodes separated by a nanogap < 15 nm. We show that functional devices including self-aligned-gate transistors, radio frequency diodes and rectifying circuits, multi-colour organic light-emitting nanodiodes and multilevel non-volatile memory devices, can be fabricated in a facile manner with minimum process complexity on a range of substrates. The compatibility of the formed nanogap electrodes with a wide range of solution processable semiconductors and substrate materials renders a-Lith highly attractive for the manufacturing of large-area nanoscale opto/electronics on arbitrary size and shape substrates.
Different clusters of Candidatus ‘Methanoperedens nitroreducens’-like archaea as revealed by high-throughput sequencing with new primers
Authors: Xu Sai , Cai Chen , Guo Jianhua , Lu Wenjing , Yuan Zhiguo , Hu Shihu
Published: May 2018

The newly discoveredCandidatus‘Methanoperedens nitroreducens’ (M.nitroreducens), mediating nitrate-dependent anaerobic oxidation of methane, is an important microorganism in linking carbon and nitrogen cycles. In order to explore the diversity ofM.nitroreducens-like archaea in various environmental niches with advanced high-throughput sequencing, new primers based on alpha subunit of methyl-coenzyme M reductase gene were designed. The PCR results demonstrated that the new primers could effectively detectM.nitroreducens-like archaea from an enrichment culture dominated byM.nitroreducensas well as samples collected from a natural freshwater lake and a full-scale wastewater treatment plant (WWTP). By high-throughput sequencing, more than 30,000M.nitroreducens-like sequences were obtained. Phylogenetic analysis of these sequences along with published sequences showed thatM.nitroreducens-like archaea could be divided into three sub-branches (named as Group A, Group B and Group C in this study). Clear geographical difference was observed, with Group A and Group B dominating samples in Queensland (Australia) and in European ecosystems, respectively. Further quantitative PCR revealed that theM.nitroreducens-like archaea were more abundant in WWTP than the freshwater lake. The study provided a large number of sequences forM.nitroreducens-like archaeal communities, thus expanded our understanding on the ecological diversity ofM.nitroreducens-like archaea.
Publisher Correction: Rice intermediate filament, OsIF, stabilizes photosynthetic machinery and yield under salinity and heat stress
Authors: Soda Neelam , Gupta Brijesh K. , Anwar Khalid , Sharan Ashutosh , Govindjee  , Singla-Pareek Sneh L. , Pareek Ashwani
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
A co-culture system of rat synovial stem cells and meniscus cells promotes cell proliferation and differentiation as compared to mono-culture
Authors: Xie Xing , Zhu Jingxian , Hu Xiaoqing , Dai Linghui , Fu Xin , Zhang Jiying , Duan Xiaoning , Ao Yingfang
Published: May 2018

A meniscus tear often happens during active sports. It needs to be repaired or replaced surgically to avoid further damage to the articular cartilage. To address the shortage of autologous meniscal cells, we designed a co-culture system of synovial stem cells (SMSCs) and meniscal cells (MCs) to produce a large cell number and to maintain characteristics of MCs. Different ratios of SMSCs and MCs at 3:1, 1:1, and 1:3 were tested. Mono-culture of SMSCs or MCs served as control groups. Proliferation and differentiation abilities were compared. The expression of extracellular matrix (ECM) genes in MCs was assessed using an ECM array to reveal the mechanism at the gene level. The co-culture system of SMSCs/MCs at the ratio of 1:3 showed better results than the control groups or those at other ratios. This co-culture system may be a promising strategy for meniscus repair with tissue engineering.
Towards a petawatt-class few-cycle infrared laser system via dual-chirped optical parametric amplification
Authors: Fu Yuxi , Midorikawa Katsumi , Takahashi Eiji J.
Published: May 2018

Expansion of the wavelength range for an ultrafast laser is an important ingredient for extending its range of applications. Conventionally, optical parametric amplification (OPA) has been employed to expand the laser wavelength to the infrared (IR) region. However, the achievable pulse energy and peak power have been limited to the mJ and the GW level, respectively. A major difficulty in the further energy scaling of OPA results from a lack of suitable large nonlinear crystals. Here, we circumvent this difficulty by employing a dual-chirped optical parametric amplification (DC-OPA) scheme. We successfully generate a multi-TW IR femtosecond laser pulse with an energy of 100 mJ order, which is higher than that reported in previous works. We also obtain excellent energy scaling ability, ultrashort pulses, flexiable wavelength tunability, and high-energy stability, which prove that DC-OPA is a superior method for the energy scaling of IR pulses to the 10 J/PW level.
Prenatal alcohol exposure increases the susceptibility to develop aggressive prolactinomas in the pituitary gland
Authors: Jabbar Shaima , Reuhl Kenneth , Sarkar Dipak K.
Published: May 2018

Excess alcohol use is known to promote development of aggressive tumors in various tissues in human patients, but the cause of alcohol promotion of tumor aggressiveness is not clearly understood. We used an animals model of fetal alcohol exposure that is known to promote tumor development and determined if alcohol programs the pituitary to acquire aggressive prolactin-secreting tumors. Our results show that pituitaries of fetal alcohol-exposed rats produced increased levels of intra-pituitary aromatase protein and plasma estrogen, enhanced pituitary tissue growth, and upon estrogen challenge developed prolactin-secreting tumors (prolactinomas) that were hemorrhagic and often penetrated into the surrounding tissue. Pituitary tumors of fetal alcohol-exposed rats produced higher levels of hemorrhage-associated genes and proteins and multipotency genes and proteins. Cells of pituitary tumor of fetal alcohol exposed rat grew into tumor spheres in ultra-low attachment plate, expressed multipotency genes, formed an increased number of colonies, showed enhanced cell migration, and induced solid tumors following inoculation in immunodeficient mice. These data suggest that fetal alcohol exposure programs the pituitary to develop aggressive prolactinoma after estrogen treatment possibly due to increase in stem cell niche within the tumor microenvironment.
Kv1.3 activity perturbs the homeostatic properties of astrocytes in glioma
Authors: Grimaldi Alfonso , D’Alessandro Giuseppina , Di Castro Maria Amalia , Lauro Clotilde , Singh Vikrant , Pagani Francesca , Sforna Luigi , Grassi Francesca , Di Angelantonio Silvia , Catacuzzeno Luigi , Wulff Heike , Limatola Cristina , Catalano Myriam
Published: May 2018

Glial cells actively maintain the homeostasis of brain parenchyma, regulating neuronal excitability and preserving the physiological composition of the extracellular milieu. Under pathological conditions, some functions of glial cells could be compromised, exacerbating the neurotoxic processes. We investigated if the homeostatic activities of astrocytes and microglia could be modulated by the voltage-gated K+ channel Kv1.3. To this end we used in vitro and in vivo systems to model cell-to-cell interactions in tumoral conditions, using a specific inhibitor of Kv1.3 channels, 5-(4-phenoxybutoxy) psoralen (PAP-1). We demonstrated that PAP-1 increases astrocytic glutamate uptake, reduces glioma-induced neurotoxicity, and decreases microglial migration and phagocytosis. We also found in a tumor blood brain barrier model that Kv1.3 activity is required for its integrity. The crucial role of Kv1.3 channels as modulators of glial cell activity was confirmed in a mouse model of glioma, where PAP-1 treatment reduces tumor volume only in the presence of active glutamate transporters GLT-1. In the same mouse model, PAP-1 reduces astrogliosis and microglial infiltration. PAP-1 also reduces tumor cell invasion. All these findings point to Kv1.3 channels as potential targets to re-instruct glial cells toward their homeostatic functions, in the context of brain tumors.