bluuebunny/crossref_metadata_2025 huggingface dataset:
How Does Vehicle To Grid Integration (V2G) Impact Energy Management And Grid Stability, And What Are The Potential Benefits And Challenges With Its Implementation?
Authors: Kalra Mankaran Singh
Published: November 2024

This research paper addresses, How Does Vehicle to Grid Integration (V2G) Impact Energy Management and Grid Stability, and What are the Potential Benefits and Challenges with its Implementation? The need to switch to electric cars (EVs) due to environmental pollution has made it difficult to manage EV energy consumption and include renewable sources. Bidirectional energy flow between EVs and the grid is made possible by Vehicle-toGrid (V2G) technology, which presents a feasible solution. The potential of V2G to optimize energy use, stabilize grids, and facilitate the integration of renewable energy sources is examined in this research. Energy Management Systems (EMS), communication networks, and bidirectional chargers are important parts. In particular, V2G is vital in areas where energy reliability is a problem. It improves grid stability, offers EV owners financial advantages, and encourages the use of renewable energy. V2G is feasible, as demonstrated by the successful deployments by companies like Nissan and Enel, despite obstacles like infrastructure requirements and battery deterioration. To fully utilize V2G,1 future developments should concentrate on standardization, policy support, and technical optimization
Factors Associated With Sedentary Behavior Among Adult Women In A Medical Clinic
Authors: Tavares Beatriz Lopes , Vieira Mariana De Sousa Nunes , Guerra Heloísa Silva
Published: November 2024

Background: Sedentary behavior (SB) refers to any behavior performed with low energy expenditure while seated, reclined, or lying down during waking hours. Considered a public health issue, SB has been associated with various adverse health outcomes. The objective of this study was to analyze factors associated with sedentary behavior in adult women attending a university medical clinic. Materials and Methods: This is a cross-sectional study with data collected from users at a medical clinic in the city of Aparecida de Goiânia. Information on sociodemographic, occupational, behavioral, and health characteristics was collected. Sedentary behavior was assessed using the short version of the International Physical Activity Questionnaire (IPAQ). Poisson multiple regression analysis with robust variance was performed. Results: The sample consisted of 223 women, and high CS was associated with an income of five or more minimum wages (p=0.021), incomplete secondary education (p=0.032), not working outside the home (p=0.047), not having children (p=0.003) and drinking alcohol twice/week (p=0.000). Conclusion: These findings indicate groups more susceptible to high sedentary behavior and can collaborate with the planning of specific interventions
The Challenges Of Inclusive Education: Reflections On Teacher Training And The Construction Of Welcoming Educational Environments
Authors: Schütz Jenerton Arlan , Júnior Edinaldo Enoque Da Silva , Bergamo Thelma Maria De Moura , Araujo Marcus Vinicius Neves , Freitas Wanderleia Maria De
Published: November 2024

Este artigo aborda os desafios da educação inclusiva, com foco na formação de professores e na construção de ambientes educacionais acolhedores. A formação docente desempenha um papel fundamental na preparação dos educadores para lidar com a diversidade em sala de aula, proporcionando-lhes ferramentas e conhecimentos necessários para implementar práticas inclusivas. Além disso, é essencial criar ambientes que acolham todos os estudantes, promovendo uma cultura de respeito e valorização das diferenças. O artigo discute as barreiras enfrentadas pelos professores, como a falta de recursos, formação continuada e apoio institucional, e apresenta reflexões sobre como superá-las, destacando a importância do desenvolvimento de competências socioemocionais e da adaptação curricular. A construção de ambientes educacionais acolhedores, que valorizam a singularidade de cada aluno, contribui para que todos se sintam incluídos e participativos, favorecendo o
A Descriptive Study To Assess The Knowledge Of Undergraduate Students Regarding The Needle Stick Injury And Its Prevention In Smt. Lakshmi Bai Batra College Of Nursing, New Delhi
Authors: Kumari Komal , Thomas Nazima , Singh Nisha
Published: November 2024

Background: A needle stick injury (NSI) is an accidental skin-penetrating stab wound from a hollow-bore needle containing another person’s blood or body fluid. Healthcare workers are at an occupational risk of exposure to blood-borne pathogens following needle stick injuries and sharp injuries. Objective: To assess the knowledge of undergraduate students regarding needle stick injuries and its prevention in Smt. Lakshmi Bai Batra College of Nursing. Method and material: The research was conducted from December 22nd, 2022 on 62 students of Smt. Lakshmi Batra College of Nursing, Delhi. A purposive sampling technique was used to select the sample and data was collected through questionnaire for accessing the knowledge regarding needle stick injuries and its prevention. Result: 62 students of Smt. Lakshmi Bai Batra College of Nursing were taken as sample using purposive sampling technique and the finding of the study indicates that knowledge regarding needle stick injury is average among 61 students and poor among 1 student and good among 0 student. Conclusion: The study indicates that poor to average knowledge regarding needle stick injury & its prevention among undergraduate students of Smt. Lakshmi Bai Batra College of Nursing
CoCl2, a mimic of hypoxia, enhances bone marrow mesenchymal stem cells migration and osteogenic differentiation via STAT3 signaling pathway
Authors: Yu Xin , Wan Qilong , Cheng Gu , Cheng Xin , Zhang Jing , Pathak Janak L. , Li Zubing
Published: June 2018

Mesenchymal stem cells homing and migration is a crucial step during bone fracture healing. Hypoxic environment in fracture site induces bone marrow mesenchymal stem cells (BMSCs) migration, but its mechanism remains unclear. Our previous study and studies by other groups have reported the involvement of signal transducer and activator of transcription 3 (STAT3) pathway in cell migration. However, the role of STAT3 pathway in hypoxia‐induced cell migration is still unknown. In this study, we investigated the role of STAT3 signaling in hypoxia‐induced BMSCs migration and osteogenic differentiation. BMSCs isolated from C57BL/6 male mice were cultured in the presence of cobalt chloride (CoCl2) to simulate intracellular hypoxia. Hypoxia enhanced BMSCs migration, and upregulated cell migration related gene expression, that is, metalloproteinase (MMP) 7, MMP9, and C‐X‐C motif chemokine receptor 4. Hypoxia enhanced the phosphorylation of STAT3, and cell migration related proteins: c‐jun n‐terminal kinase (JNK), focal of adhesion kinase (FAK), extracellular regulated protein kinases, and protein kinase B 1/2 (ERK1/2). Moreover, hypoxia enhanced expression of osteogenic differentiation marker. Inhibition of STAT3 suppressed the hypoxia‐induced BMSCs migration, cell migration related signaling molecules phosphorylation, and osteogenic differentiation related gene expression. In conclusion, our result indicates that hypoxia‐induced BMSCs migration and osteogenic differentiation is via STAT3 phosphorylation and involves the cooperative activity of the JNK, FAK, and MMP9 signaling pathways.
Why is HMBC superior to LR‐HSQC? Influence of homonuclear couplings JHH′ on the intensity of long‐range correlations
Authors: Bigler Peter , Furrer Julien
Published: June 2018

Long‐range heteronuclear single quantum correlation (LR‐HSQC) experiments may be applied as an alternative to heteronuclear multiple‐bond correlation (HMBC) experiments for detecting long‐range correlations but has never enjoyed popularity for that purpose. To the best of our knowledge, the exact reasons have not yet been fully established. For both experiments, it is widely accepted that the evolution of proton–proton homonuclear couplings JHH′ during the polarization transfer delays Δ leads to significant losses, and that the intensity of the observable coherence is zero when JHH′ matches the condition Δ = 0.5/JHH′. Here, we analyze the influence of JHH′ on the intensity of long‐range correlations in HMBC and LR‐HSQC spectra. We show that for both experiments long‐range correlations will not be canceled because of homonuclear couplings JHH′. Our theoretical and experimental results definitely establish and validate the superiority of HMBC‐based experiments among the family of heteronuclear long‐range correlation experiments: (a) the overall cross peak's intensity is higher, and (b) in LR‐HSQC experiments, the intensity of the long‐range cross peaks is additionally influenced in an unwanted way by the magnitude and number of passive homonuclear proton–proton couplings JHH′.
Mutational analysis of the pro‐peptide of a marine intracellular subtilisin protease supports its role in inhibition
Authors: Bjerga Gro E. K. , Larsen Øivind , Arsın Hasan , Williamson Adele , García‐Moyano Antonio , Leiros Ingar , Puntervoll Pål
Published: June 2018

Intracellular subtilisin proteases (ISPs) have important roles in protein processing during the stationary phase in bacteria. Their unregulated protein degrading activity may have adverse effects inside a cell, but little is known about their regulatory mechanism. Until now, ISPs have mostly been described from Bacillus species, with structural data from a single homolog. Here, we study a marine ISP originating from a phylogenetically distinct genus, Planococcus sp. The enzyme was successfully overexpressed in E. coli, and is active in presence of calcium, which is thought to have a role in minor, but essential, structural rearrangements needed for catalytic activity. The ISP operates at alkaline pH and at moderate temperatures, and has a corresponding melting temperature around 60 °C. The high‐resolution 3‐dimensional structure reported here, represents an ISP with an intact catalytic triad albeit in a configuration with an inhibitory pro‐peptide bound. The pro‐peptide is removed in other homologs, but the removal of the pro‐peptide from the Planococcus sp. AW02J18 ISP appears to be different, and possibly involves several steps. A first processing step is described here as the removal of 2 immediate N‐terminal residues. Furthermore, the pro‐peptide contains a conserved LIPY/F‐motif, which was found to be involved in inhibition of the catalytic activity.
Trace water mediated growth of oriented single-crystalline mesoporous metal–organic frameworks on gold nanorods
Authors: Zhou Zehao , Li Mengyuan , Zhao Jian , Di Zhenghan , Di Chunzhi , Liu Bei , Zhang Chao , Yan Chun-Hua , Li Lele
Published: June 2018

The growth of single-crystalline mesoporous MOFs with well-controlled orientation on the surface of gold nanorods was reported for the first time.
Heteroatomic interface engineering in MOF-derived carbon heterostructures with built-in electric-field effects for high performance Al-ion batteries
Authors: Li Caixia , Dong Shihua , Tang Rui , Ge Xiaoli , Zhang Zhiwei , Wang Chengxiang , Lu Yupeng , Yin Longwei
Published: June 2018

By controllable heteroatomic interface engineering, a MOF-derived gradient N,P-doped C@N-C@N,P-C heterostructure with built-in electric field was acquired.
Theory for polariton-assisted remote energy transfer
Authors: Du Matthew , Martínez-Martínez Luis A. , Ribeiro Raphael F. , Hu Zixuan , Menon Vinod M. , Yuen-Zhou Joel
Published: June 2018

A comprehensive theory is presented to mechanistically elucidate the long-range energy transfer between molecules strongly coupled to electromagnetic fields.
Efficient and UV-stable perovskite solar cells enabled by side chain-engineered polymeric hole-transporting layers
Authors: Tsai Chang-Hung , Li Nan , Lee Chia-Chen , Wu Hung-Chin , Zhu Zonglong , Wang Liduo , Chen Wen-Chang , Yan He , Chueh Chu-Chen
Published: June 2018

Biaxially-extended octithiophene-based conjugated polymers are demonstrated as effective polymeric hole-transporting layers to simultaneously enhance efficiency and UV-photostability of perovskite solar cells.
Bergenin loaded gum xanthan stabilized silver nanoparticles suppress synovial inflammation through modulation of the immune response and oxidative stress in adjuvant induced arthritic rats
Authors: Rao Komal , Roome Talat , Aziz Sabahat , Razzak Anam , Abbas Ghulam , Imran Muhammad , Jabri Tooba , Gul Jasra , Hussain Munawar , Sikandar Bushra , Sharafat Shaheen , Shah Muhammad Raza
Published: June 2018

Bergenin (BG) is a naturally occurring C-glycoside with demonstrated anti-arthritic potential.
3D printing of ceramic-based scaffolds for bone tissue engineering: an overview
Authors: Du Xiaoyu , Fu Shengyang , Zhu Yufang
Published: June 2018

In this review, we systematically highlight the advances in 3D printing of ceramic-based scaffolds for bone tissue engineering.
An intelligent and biocompatible photosensitizer conjugated silicon quantum dots–MnO2 nanosystem for fluorescence imaging-guided efficient photodynamic therapy
Authors: Wang Rong-gui , Zhao Meng-yao , Deng Di , Ye Xin , Zhang Fan , Chen Hui , Kong Ji-lie
Published: June 2018

We constructed an intelligent and biocompatible BSA–Ce6–Si QDs–MnO2 nanocomplex as a pH/H2O2 responsive photosensitizer nanocarrier for fluorescence imaging-guided photodynamic therapy (PDT).
Radial velocity estimation of moving target based on maximum likelihood estimation
Authors: Gao Yesheng , Guo Xiaojiang , Liu Xingzhao
Published: June 2018

For conventional multichannel synthetic aperture radar (SAR) systems, the pulse repetition frequency is greater than the azimuth Doppler bandwidth. Therefore, each receive channel can obtain unambiguous SAR image and the moving target usually overlaps with no more than one clutter. However, for high‐resolution wide‐swath (HRWS) SAR systems, the PRF is usually much less than the Doppler bandwidth and thus the moving target may overlap with quite a few clutters, which will severely affect the estimation of the radial velocity of the moving target. A novel radial velocity estimation method based on maximum likelihood estimation (MLE) for HRWS SAR systems is presented. Even if the moving target overlaps with quite a few clutters, the proposed MLE method can still effectively estimate the radial velocity. In order to reduce the computational load, the proposed method transforms the multi‐dimensional spectral peak searching of MLE into one‐dimensional peak searching and reduces the times of matrix inversion by a block matrix method. Theoretical analysis and experiments demonstrate the feasibility of the proposed method.
A Familial Case of Multicentric Carpotarsal Osteolysis Syndrome and Treatment Outcome
Authors: Gomes Alicia , Weiser Peter , Descartes Maria , Upadia Jariya
Published: June 2018

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder caused by heterozygous mutations in the MAFB gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B). This is an autosomal dominant condition with a high frequency of sporadic cases. MCTO is characterized by osteolysis of the carpal, metacarpal, and tarsal bones beginning in early childhood with musculoskeletal rheumatologic symptoms such as pain and disability. Renal involvement can be seen in more than half of the patients; from ages 16 months to 42 years and manifests from proteinuria to end-stage renal failure requiring renal transplantation. The association of MAFB gene mutations with this genetic condition has aided in understanding the pathophysiology of the disease. We report here a 7-year-old Caucasian boy and his 33-year-old mother diagnosed with MCTO, with the boy having concomitant juvenile idiopathic arthritis. He was initially diagnosed with arthritis at age 5 years based on bilateral wrist synovial swelling, morning stiffness, and weakness with family history of his mother being diagnosed with erosive psoriatic arthritis leading to limb deformities. Initial therapy for the boy included methotrexate and infliximab with moderate response. Later, during the course of his disease, he underwent a genetic evaluation at age 7 years for history of learning disabilities and dysmorphic features. Maternal evaluation and radiographic examination led to a clinical diagnosis of MCTO in the mother, and subsequent testing for MAFB gene in the son revealed a mutation at c.206C > T (p.Ser69Leu), the most commonly reported genetic change in MCTO. Nevertheless, further imaging still confirmed ongoing arthritis, and therapy was adjusted based on its progression including abatacept, tocilizumab, and pamidronate. Our report highlights the possibility of concomitant inflammatory arthropathy in MCTO.
Robotic-Assisted Sleeve Lobectomy Using the Four-Arm Technique in the DaVinci Si® and Xi® Systems
Authors: Egberts Jan-Hendrik , Möller Thorben , Becker Thomas
Published: June 2018

Sleeve lobectomy (SL) makes it possible to resect centrally located lung carcinoma oncological correct while protecting healthy lung tissue. However, this procedure is often limited with conventional video-assisted thoracoscopic surgery, due to the limited mobility of the rigid and long instruments and the limited visualization. Therefore, these interventions are often still performed in the open conventional technique with the well-known disadvantages. Particularly in the reconstruction of the respiratory tract, precise sewing must be performed in a small space to avoid stenosis of the different diameter of the lumina. Robotic surgery offers several advantages through an enlarged three-dimensional view and flexibility of the robotic instruments, which are particularly evident when sewing. So far, there are only a few reports of robotic SL. Here, we describe our experience of performing robotic SL with four arms on both, the currently available DaVinci Xi® and Si® systems.
Lack of Association of Intraventricular Hemorrhage with Retinopathy of Prematurity
Authors: Hand Ivan , Shrier Eric
Published: June 2018

Objective Retinopathy of prematurity (ROP) is the primary cause of visual impairment in premature infants. Our objective was to study the relationship between ROP and intraventricular hemorrhage (IVH) in the premature infant.

Methods This study was a retrospective chart review of very low birthweight infants of 1,500 g or less admitted to Kings County Hospital Center's neonatal intensive care unit who were screened for ROP over a 6-year period.

Results Of 335 infants screened for ROP, 85 infants were identified to have ROP. Of these, 50 (56%) infants had stage 1 ROP, 25 (29%) had stage 2 ROP, 7 (8%) had stage 3 ROP, and 3 (4%) had stage 4 ROP. The incidence of IVH in our population was 14%. Multiple logistic regression demonstrated a significant association between ROP and gestational age (p = 0.001). There was no significant association between ROP stage and IVH grade. There was also no significant association between birthweight, ethnicity, or 5-minute Apgar score.

Conclusions Our data demonstrated no association between IVH and severity of ROP. There was a statistically significant association between ROP and gestational age. We speculate that these data may be a reflection of improvement in neonatal care, with a declining incidence of IVH as well as increased ROP screening efforts.
Gaiareveals evidence for merged white dwarfs
Authors: Kilic Mukremin , Hambly N C , Bergeron P , Genest-Beaulieu C , Rowell N
Published: June 2018

We use Gaia Data Release 2 to identify 13 928 white dwarfs (WDs) within 100 pc of the Sun. The exquisite astrometry from Gaia reveals for the first time a bifurcation in the observed WD sequence in both Gaia and the Sloan Digital Sky Survey (SDSS) passbands. The latter is easily explained by a helium atmosphere WD fraction of 36 per cent. However, the bifurcation in the Gaia colour–magnitude diagram depends on both the atmospheric composition and the mass distribution. We simulate theoretical colour–magnitude diagrams for single and binary WDs using a population synthesis approach and demonstrate that there is a significant contribution from relatively massive WDs that likely formed through mergers. These include WD remnants of main-sequence (blue stragglers) and post-main-sequence mergers. The mass distribution of the SDSS subsample, including the spectroscopically confirmed WDs, also shows this massive bump. This is the first direct detection of such a population in a volume-limited sample.
Characterization of nonlinear receptive fields of visual neurons by convolutional neural network
Authors: Ukita Jumpei , Yoshida Takashi , Ohki Kenichi
Published: June 2018

A comprehensive understanding of the stimulus-response properties of individual neurons is necessary to crack the neural code of sensory cortices. However, a barrier to achieving this goal is the difficulty of analyzing the nonlinearity of neuronal responses. In computer vision, artificial neural networks, especially convolutional neural networks (CNNs), have demonstrated state-of-the-art performance in image recognition by capturing the higher-order statistics of natural images. Here, we incorporated CNN for encoding models of neurons in the visual cortex to develop a new method of nonlinear response characterization, especially nonlinear estimation of receptive fields (RFs), without assumptions regarding the type of nonlinearity. Briefly, after training CNN to predict the visual responses of neurons to natural images, we synthesized the RF image such that the image would predictively evoke a maximum response (“maximization-of-activation” method). We first demonstrated the proof-of-principle using a dataset of simulated cells with various types of nonlinearity, revealing that CNN could be used to estimate the nonlinear RF of simulated cells. In particular, we could visualize various types of nonlinearity underlying the responses, such as shift-invariant RFs or rotation-invariant RFs. These results suggest that the method may be applicable to neurons with complex nonlinearities, such as rotation-invariant neurons in higher visual areas. Next, we applied the method to a dataset of neurons in the mouse primary visual cortex (V1) whose responses to natural images were recorded via two-photon Ca2+ imaging. We could visualize shift-invariant RFs with Gabor-like shapes for some V1 neurons. By quantifying the degree of shift-invariance, each V1 neuron was classified as either a shift-variant (simple) cell or shift-invariant (complex-like) cell, and these two types of neurons were not clustered in cortical space. These results suggest that the novel CNN encoding model is useful in nonlinear response analyses of visual neurons and potentially of any sensory neurons.
Frequent translation of small open reading frames in evolutionary conserved lncRNA regions
Authors: Ruiz-Orera Jorge , Albà M.Mar
Published: June 2018

The mammalian transcriptome includes thousands of transcripts that do not correspond to annotated protein-coding genes. Although many of these transcripts show homology between human and mouse, only a small proportion of them have been functionally characterized. Here we use ribosome profiling data to identify translated open reading frames, as well as non-ribosomal protein-RNA interactions, in evolutionary conserved and non-conserved transcripts. We find that conserved regions are subject to significant evolutionary constraints and are enriched in translated open reading frames, as well as non-ribosomal protein-RNA interaction signatures, when compared to non-conserved regions. Translated ORFs can be divided in two classes, those encoding functional micropeptides and those that show no evidence of protein functionality. This study underscores the importance of combining evolutionary and biochemical measurements to advance in a more complete understanding of the transcriptome.
The effects of drought and nutrient addition on soil organisms vary across taxonomic groups, but are constant across seasons
Authors: Siebert Julia , Sünnemann Marie , Auge Harald , Berger Sigrid , Cesarz Simone , Ciobanu Marcel , Guerrero-Ramírez Nathaly R. , Eisenhauer Nico
Published: June 2018

Anthropogenic global change alters the activity and functional composition of soil communities that are responsible for crucial ecosystem functions and services. Two of the most pervasive global change drivers are drought and nutrient enrichment. However, the responses of soil organisms to interacting global change drivers remain widely unknown. We tested the interactive effects of extreme drought and fertilization on soil biota ranging from microbes to invertebrates across seasons. We expected drought to reduce the activity of soil organisms and fertilization to induce positive bottom-up effectsviaincreased plant productivity. Furthermore, we hypothesized fertilization to reinforce drought effects through enhanced plant growth, resulting in even dryer soil conditions. Our results revealed that drought had detrimental effects on soil invertebrate feeding activity and simplified nematode community structure, whereas soil microbial activity and biomass were unaffected. Microbial biomass increased in response to fertilization, whereas invertebrate feeding activity substantially declined. Notably, these effects were consistent across seasons. The dissimilar responses suggest that soil biota differ vastly in their vulnerability to global change drivers. As decomposition and nutrient cycling are driven by the interdependent concurrence of microbial and faunal activity, this may imply far-reaching consequences for crucial ecosystem processes in a changing world.
Regulation of the Unfolded Protein Response by BiP AMPylation protects photoreceptors from light-dependent degeneration
Authors: Moehlman Andrew T. , Casey Amanda K. , Servage Kelly , Orth Kim , Krämer Helmut
Published: June 2018

In response to environmental, developmental, and pathological stressors, cells engage homeostatic pathways to maintain their function. Among these pathways, the Unfolded Protein Response protects cells from the accumulation of misfolded proteins in the ER. Depending on ER stress levels, the ER-resident Fic protein catalyzes AMPylation or de-AMPylation of BiP, the major ER chaperone and regulator of the Unfolded Protein Response. This work elucidates the importance of the reversible AMPylation of BiP in maintaining theDrosophilavisual system in response to stress. After 72 hours of constant light, photoreceptors offic-null and AMPylation-resistantBiPT366Amutants, but not wild-type flies, display loss of synaptic function, disintegration of rhabdomeres, and excessive activation of ER stress reporters. Strikingly, this phenotype is reversible: photoreceptors regain their structure and function within 72 hours once returned to a standard light:dark cycle. These findings show that Fic-mediated AMPylation of BiP is required for neurons to adapt to transient stress demands.
Predicting and Analyzing the Response to Selection on Correlated Characters
Authors: Van Dooren Tom J.M , Allen Cerisse E. , Beldade Patrícia
Published: June 2018

The breeder’s equation generally provides robust predictions for the short-term evolution of single characters. When selection targets two or more characters simultaneously, there are often large discrepancies between predicted and observed responses. We assessed how well this standard model predicts responses to bivariate selection on wing color pattern characteristics in the tropical butterflyBicyclus anynana. In separate laboratory selection experiments, two sets of serially repeated eyespots were subjected to ten generations of concerted and antagonistic selection for either size or color composition. We compared predicted and actual selection responses over successive generations, using the phenotypic data, selection differentials, and estimates of the genetic variance-covariance matrixG. We found differences in the precision of predictions between directions of selection but did not find any evidence of systematic biases in our predictions depending on the direction of selection. Our investigation revealed significant environmental effects on trait evolution across generations. When these were accounted for, predictions using the standard model improved considerably. In the experiment on eyespot size, secondary splitting of selection lines allowed the estimation of changes inGafter nine generations of selection. Changes were not in general agreement with expectations from the breeder’s equation. A contour plot of prediction errors across trait space suggests that directional epistasis in the eyespot genotype-phenotype map might occur but estimates of changes inGare too model-dependent to verify whether they agree with that hypothesis. Altogether, our results underscore the need for quantitative genetics to investigate and estimate potential effects of multivariate non-linear genotype-phenotype maps and of environmental effects onG.
A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes
Authors: Sun Yan , Kim Eun Ji , Felt Sébastien A. , Taylor Louis J. , Agarwal Divyansh , Grant Gregory R. , López Carolina B.
Published: June 2018

Defective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) bothin vitroandin vivo.However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to manipulate cbDVG content in order to modulate the host response to infection. Here we report a specific genomic signal that mediates the generation of RSV cbDVGs. Using a customized bioinformatics tool, we identified regions in the RSV genome frequently used to generate cbDVGs during infection. We then created a minigenome system to validate the function of one of these sequences and to determine if specific nucleotides were essential for cbDVG generation at that position. Further, we created a recombinant virus that selectively produced a specific cbDVG based on variations introduced in this sequence. The identified sequence was also found as a common site for cbDVG generation during natural RSV infections, and common cbDVGs generated at this sequence were found among samples from various infected patients. These data demonstrate that sequences encoded in the viral genome are critical determinants of the location of cbDVG generation and, therefore, this is not a stochastic process. Most importantly, these findings open the possibility of genetically manipulating cbDVG formation to modulate infection outcome.

Author summary

Copy-back defective viral genomes (cbDVGs) regulate infection and pathogenesis ofMononegavirales.cbDVG are believed to arise from random errors that occur during virus replication and the predominant hypothesis is that the viral polymerase is the main driver of cbDVG generation. Here we describe a specific genomic sequence in the RSV genome that is necessary for the generation of a large proportion of the cbDVG population present during infection. We identified specific nucleotides that when modified altered cbDVG generation at this position, and we created a recombinant virus that selectively produced cbDVGs based on mutations in this sequence. These data demonstrate that the generation of RSV cbDVGs is regulated by specific viral sequences and that these sequences can be manipulated to alter the content and quality of cbDVG generated during infection.
14-3-3 recruits keratin intermediate filaments to mechanically sensitive cell-cell contacts
Authors: Mariani Richard A. , Paranjpe Shalaka , Dobrowolski Radek , Weber Gregory F.
Published: June 2018

Abstract

Intermediate filament cytoskeletal networks simultaneously support mechanical integrity and influence signal transduction pathways. Marked remodeling of the keratin intermediate filament network accompanies collective cellular morphogenetic movements that occur during early embryonic development in the frogXenopus laevis. While this reorganization of keratin is initiated by force transduction on cell-cell contacts mediated by C-cadherin, the mechanism by which keratin filament reorganization occurs remains poorly understood. In this work we demonstrate that 14-3-3 proteins regulate keratin reorganization dynamics in embryonic mesendoderm cells fromXenopusgastrula. 14-3-3 co-localizes with keratin filaments near cell-cell junctions in migrating mesendoderm. Co-immunoprecipitation, mass spectrometry and bioinformatic analyses indicate Keratin 19 is a target of 14-3-3 in the whole embryo and, more specifically, mesendoderm tissue. Inhibition of 14-3-3 results in both the decreased exchange of keratin subunits into filaments and blocks keratin filament recruitment toward cell-cell contacts. Synthetically coupling 14-3-3 to Keratin 19 through a unique fusion construct conversely induces the localization of this keratin population to the region of cell-cell contacts. Taken together, these findings indicate that 14-3-3 acts on keratin intermediate filaments and is involved in their reorganization to sites of cell adhesion.
Reassociation of an invasive plant with its specialist herbivore provides a test of the shifting defence hypothesis
Authors: Wan Jinlong , Huang Bei , Yu Hua , Peng Shaolin
Published: June 2018

The shifting defence hypothesis (SDH) predicts that after invasive plants are introduced to new ranges, they will evolve reduced resistance to specialist herbivores and increased resistance to generalist herbivores because they can escape from specialists but are still attacked by generalists in their nonnative ranges. For this to be true, the subsequent introduction of native specialist herbivores should reverse the above evolutionary processes, but evidence collected so far is scarce.

Here, we address this research gap by comparing resistance to specialist and generalist herbivores and resistance‐related traits in the invasive plant Ambrosia artemisiifolia from five populations with about a decade history of infestation by the accidentally introduced native specialist leaf beetle Ophraella communa (infested populations), and three populations without such infestation history (uninfested populations).

In common garden experiments, the specialist O. communa performed better on uninfested populations than on infested populations, whereas two generalist insects, Spodoptera litura and Helicoverpa armigera, performed better on infested populations. Chemical analyses showed that plants from infested populations had lower concentrations of chlorogenic acid, an antigeneralist secondary compound that can attract O. communa. Furthermore, across mother plants from all populations studied, chlorogenic acid content was negatively correlated with larval growth of S. litura and positively correlated with that of O. communa. Finally, quantitative defence traits did not differ between infested and uninfested populations.

Although our results are most consistent with rapid evolution caused by enemy reassociation, we cannot exclude the possibility that observed differences in resistance result from multiple introductions or selections from other environmental factors.

Synthesis. These results suggest that reassociation with a specialist herbivore from the native range may result in a rapid evolution of increased resistance to specialist herbivores and reduced resistance to generalist herbivores in the introduced range, which is likely to be mediated by the reduced production of secondary chemicals that can deter generalists while attracting the introduced specialist. This study supports the shifting defence hypothesis (SDH) from a new viewpoint, emphasizing the importance of incorporating the impacts of both specialist and generalist herbivores when evaluating the long‐term control effects of classical biological control programmes.
Glycyrrhizin has a high likelihood to be a victim of drug–drug interactions mediated by hepatic organic anion‐transporting polypeptide 1B1/1B3
Authors: Dong Jiajia , Olaleye Olajide E , Jiang Rongrong , Li Jing , Lu Chuang , Du Feifei , Xu Fang , Yang Junling , Wang Fengqing , Jia Weiwei , Li Chuan
Published: June 2018

Background and Purpose

Intravenous glycyrrhizin, having anti‐inflammatory and hepatoprotective properties, is incorporated into the management of liver diseases in China. This investigation was designed to elucidate the molecular mechanism underlying hepatobiliary excretion of glycyrrhizin and to investigate its potential for drug–drug interactions on organic anion‐transporting polypeptide (OATP)1B.

Experimental Approach

Human transporters mediating hepatobiliary excretion of glycyrrhizin were characterized at the cellular and vesicular levels and compared with rat hepatic transporters. The role of Oatp1b2 in glycyrrhizin's elimination and pharmacokinetics was evaluated in rats using the inhibitor rifampin. A physiologically based pharmacokinetic (PBPK) model for glycyrrhizin, incorporating transporter‐mediated hepatobiliary excretion, was established and applied to predict potential drug–drug interactions related to glycyrrhizin in humans.

Key Results

Hepatobiliary excretion of glycyrrhizin involved human OATP1B1/1B3 (Oatp1b2 in rats)‐mediated hepatic uptake from blood and human multidrug resistance‐associated protein (MRP)2/breast cancer resistance protein (ABCP)/bile salt export pump (BSEP)/multidrug resistance protein 1 (Mrp2/Abcp/Bsep in rats)‐mediated hepatic efflux into bile. In rats, rifampin impaired hepatic uptake of glycyrrhizin significantly increasing its systemic exposure. Glomerular‐filtration‐based renal excretion of glycyrrhizin was slow due to extensive protein binding in plasma. Quantitative analysis using the PBPK model demonstrated that OATP1B1/1B3 have critical roles in the pharmacokinetics of glycyrrhizin, which is highly likely to be a victim of drug–drug interactions when co‐administered with potent dual inhibitors of these transporters.

Conclusions and Implications

Transporter‐mediated hepatobiliary excretion governs glycyrrhizin's elimination and pharmacokinetics. Understanding glycyrrhizin's potential drug–drug interactions on OATP1B1/1B3 should enhance the therapeutic outcome of glycyrrhizin‐containing drug combinations on liver diseases.
Adenosine 5'‐monophosphate‐activated protein kinase‐dependent mTOR pathway is involved in flavokawain B‐induced autophagy in thyroid cancer cells
Authors: He Qin , Liu Wenping , Sha Sha , Fan Shanshan , Yu Yajing , Chen Li , Dong Ming
Published: June 2018

Flavokawain B (FKB), a natural kava chalcone, shows potent antitumor activity in various types of cancer, although the mechanism of action remains unclear. In this study, we report that FKB has profound effects on the metabolic state of human thyroid cancer (TCa) cells, leading to high autophagy flux through upregulation of AMP‐activated protein kinase, which in turn inhibits mTOR and activates Beclin‐1 in TCa cells. We further report that the autophagy induced by FKB plays a prosurvival role in TCa cells both in vitro and in vivo. In conclusion, our findings provide evidence that combination treatment with FKB and pharmacological autophagy inhibitors will be a potential therapeutic strategy for the treatment of TCa.
Morphology quiz: Identification of the origin of metastatic cells in pleural effusion
Authors: Frankel D. , Robaglia‐Schlupp A. , Bourlard D. , Kaspi E. , Roll P.
Published: June 2018

Test yourself in this educational case establishing the nature of the cells present in a pleural effusion of a patient with history of previous skin cancer.
Diabetes associated with immune checkpoint inhibition: presentation and management challenges
Authors: Galligan A. , Xu W. , Fourlanos S. , Nankervis A. , Chiang C. , Mant A. M. , Parente P. , Rischin D. , Krishnamurthy B. , Sandhu S. , Colman P. G.
Published: June 2018

Background

In recent years, immune checkpoint blockade has become a standard therapy for a wide range of cancers. Adverse events, including endocrinopathies, result from the induction of autoimmunity.

Case report

We report a case series of nine individuals who presented with immunotherapy‐induced Type 1 diabetes between 2015 and 2017. Onset of diabetes occurred within 12 weeks of commencing therapy. Anti‐glutamic acid decarboxylase antibodies were present in six people. Retrospective testing of islet antibodies in pre‐treatment samples was possible in two people and this revealed anti‐glutamic acid decarboxylase seroconversion in the first and high anti‐glutamic acid decarboxylase titres pre‐ and post‐treatment in the second person. Six people had high risk human leukocyte antigen haplotypes. Clinical and genetic factors are described and compared with previously published cases.

Conclusion

This rare form of iatrogenic diabetes is a result of an accelerated, fulminant islet autoimmunity induced by immune checkpoint inhibitors. High risk human leukocyte antigen haplotypes have been found in the majority of cases. The role of pre‐existing islet autoantibodies as a biomarker is not yet known.
Body mass index and the risk of mortality among Chinese adults with Type 2 diabetes
Authors: Xu H. , Zhang M. , Xu D. , Zhang F. , Yao B. , Yan Y. , Zhao N. , Xu W. , Qin G.
Published: June 2018

Aims

To examine the associations between BMI and the risks of all‐cause, cardiovascular disease (CVD)‐specific and cancer‐specific mortality among people with Type 2 diabetes, and thus provide recommendations for weight management in the population.

Methods

This retrospective cohort study was conducted among 52 763 people with newly diagnosed Type 2 diabetes between 1 January 2004 and 31 December 2014 in Shanghai, China. All cases of death were identified by linking to the Shanghai Vital Statistics. Some 52 488 people were included in the analysis. Survival curves for people with different BMI categories were plotted using the Kaplan–Meier method. Cox proportional hazard models within or without restricted cubic spline functions were applied to examine the potential non‐linear or linear relationship between BMI and the risk of mortalities respectively.

Results

A total of 4777 deaths were identified during an average of 6‐year follow‐up. An L‐shaped association was observed between BMI and all‐cause mortality in men (P for overall association < 0.001 and P for non‐linearity < 0.001) while a U‐shaped association was found in women (P for overall association < 0.001 and P for non‐linearity< 0.001). In men, no significant association was observed for BMI with cancer‐specific and CVD‐specific mortality. In women, an increased risk of cancer‐specific mortality was observed with increasing BMI, whereas decreasing BMI was associated with the increased CVD‐specific mortality rate.

Conclusion

The increased all‐cause mortality in men with low BMI and in women with either low or high BMI indicate the importance of keeping BMI in a normal range for Chinese adults with Type 2 diabetes.
Extranodal NK/T‐cell lymphoma, nasal type: Clinical features, outcome, and prognostic factors in 101 cases
Authors: Su Yi‐Jiun , Wang Po‐Nan , Chang Hung , Shih Lee‐Yung , Lin Tung‐Liang , Kuo Ming‐Chung , Chuang Wen‐Yu , Wu Jin‐Hou , Tang Tzung‐Chih , Hung Yu‐Shin , Dunn Po , Kao Hsiao‐Wen
Published: June 2018

Objectives

We aimed to define the clinical features, outcome, and prognostic factors for extranodal NK/T‐cell lymphoma (ENKTL) patients in Taiwan.

Methods

We retrospectively reviewed 101 ENKTL patients diagnosed between February 1998 and October 2015.

Results

The median age of 101 patients was 52 years old (range 22‐85); 76.2% of patients were Ann Arbor stage I/II disease. The 5‐year progression‐free survival (PFS) and overall survival (OS) were 49.9% and 54.8%, respectively. Patients with log[EBV‐DNA] ≥ 3.8 and bone marrow hemophagocytosis at diagnosis had inferior PFS and OS. Most stage I/II patients received combined chemoradiotherapy with anthracycline‐containing regimen, with overall response rate of 96.7%, complete response rate 86.9%, 5‐year PFS 65%, and OS 72%. The relapse rate was 29.3% with a short median disease‐free survival of 6.2 months. In advanced stage patients, overall response rate was only 13.6%, with median PFS 2.3 months, and OS 4.8 months. Age ≥ 60 (HR 3.773, 95% CI 1.733‐8.215, P = 0.001) and stage III/IV (HR 7.785, 95% CI 2.312‐26.213, P = 0.001) were unfavorable prognostic factors for PFS and OS by multivariate analyses.

Conclusions

Age ≥ 60 and stage III/IV are independent poor prognostic factors for PFS and OS. Early‐stage ENKTL patients had good response to combined chemoradiotherapy with anthracycline‐containing regimen but with a high relapse rate and short disease‐free survival. Anthracycline‐containing regimen in advanced stage had poor response and dismal outcome.
Combined fractional carbon dioxide laser and long‐pulsed neodymium : yttrium‐aluminium‐garnet (1064 nm) laser in treatment of hidradenitis suppurativa; a prospective randomized intra‐individual controlled study
Authors: Abdel Azim Amira A. , Salem Rania T. , Abdelghani Rania
Published: June 2018

Background

Multiple treatment modalities were introduced for treatment of hidradenitis suppurativa (HS) but mostly with unsatisfactory results.

Objective

In this prospective randomized right‐left intra‐individual controlled study, we studied the safety and efficacy of combined treatment with fractional CO2 laser and long pulsed Nd : YAG (1064 nm) laser in treatment of HS.

Methods

Twenty adult patients with HS were randomized into this study. The patients were randomly allocated to receive four laser sessions with 2 weeks interval. Control side received long pulsed Nd : YAG laser (1064 nm) only, and the other side (combined treatment side) received combined fractional CO2 laser and long pulsed Nd : YAG (1064 nm) laser. Patients were clinically and histopathologically evaluated 2 weeks post treatment. Recurrence was evaluated 3 months post treatment. Outcome was clinically evaluated by physician global assessment (PGA), 10‐point visual analog scale for patient's satisfaction, and side effects.

Results

Statistically significant higher improvement and patient's satisfaction was observed in combined treatment side compared with control side (P = 0.011, 0.048 respectively). Absence of recurrence was achieved by 55% of sides receiving combined treatment and 35% of control sides.

Conclusions

Combination of fractional CO2 laser and long pulsed Nd : YAG (1064 nm) laser in treatment of HS had higher improvement and patient's satisfaction together with lower recurrence compared with long pulsed Nd : YAG (1064 nm) laser alone. Better results could be achieved with low PGA, non‐obese populations, and absence of surgeries for the lesions.
Evaluation of intralesional injection of bleomycin in the treatment of plantar warts: clinical and dermoscopic evaluation
Authors: Barkat Manal T. , Abdel‐Aziz Rasha T. A. , Mohamed Mervat S.
Published: June 2018

Background

Treatment of plantar warts is difficult and requires multiple treatments, and they are more refractory to treatment than common warts. Intralesional bleomycin has been used in the treatment of warts with varying degrees of success.

Aim

The aim of the present work is to evaluate the efficacy of intralesional injection of bleomycin in the treatment of plantar warts based on clinical and dermoscopic observations.

Patients and methods

Bleomycin (1 mg/ml) was injected intralesionally into the pared plantar wart every 2 weeks for a maximum of four sessions. Patients were followed both clinically and by the use of dermoscope.

Results

The cure rate of plantar warts treated with bleomycin was 69.3% with minimal and tolerable side effects.

Conclusion

Intralesional injection of bleomycin is an effective and safe treatment of plantar warts. Dermoscope is recommended in the evaluation of treatment success, as it can accurately tell if the wart needs further treatment, preventing premature stoppage of the treatment, thus decreasing the possibility of recurrences.