bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiating the Roles of UL16, UL21 and Us3 in the Nuclear Egress of Herpes Simplex Virus Capsids
Authors: Gao Jie , Finnen Renée L. , Sherry Maxwell R. , Le Sage Valerie , Banfield Bruce W. 
Published: February 2020

AbstractPrevious studies from our laboratory established that pUL16 and pUL21 are required for efficient nuclear egress of herpes simplex type 2 (HSV-2) capsids. To better understand the role of these proteins in nuclear egress, we wished to establish whether nuclear egress complex (NEC) localization and/or function was altered in the absence of either pUL16 or pUL21. We used antiserum raised against HSV-2 NEC components pUL31 and pUL34 to examine NEC localization by immunofluorescence microscopy. NEC localization in cells infected with pUL16 deficient viruses was indistinguishable from that observed in cells infected with wild type viruses. By contrast, NEC localization was found to be aberrant in cells infected with pUL21 deficient virus and, instead, showed some similarity to the aberrant NEC localization pattern observed in cells infected with pUs3 deficient virus. These results indicated that pUL16 plays a role in nuclear egress that is distinct from that of pUL21 and pUs3. Higher resolution examination of nuclear envelope ultrastructure in cells infected with pUL21 deficient viruses by transmission electron microscopy showed different types of nuclear envelope perturbations, including some that were not observed in cells infected with pUs3 deficient virus. The formation of the nuclear envelope perturbations observed in pUL21 deficient virus infections was found to be dependent on a functional NEC, revealing a novel role for pUL21 in regulating NEC activity. The results of comparisons of nuclear envelope ultrastructure in cells infected with viruses lacking pUs3, pUL16 or both pUs3 and pUL16 were consistent with a role for pUL16 upstream of primary capsid envelopment and shed new light on how pUs3 functions in nuclear egress.Author summaryThe membrane deformation activity of the herpesvirus nuclear egress complex (NEC), allows viral capsids to transit from their site of assembly in the nucleus through both nuclear membranes into the cytoplasm. The timing, extent and directionality of NEC activity must be precisely controlled during viral infection, yet our knowledge of how NEC activity is controlled is incomplete. To determine how pUL16 and pUL21, two viral proteins required for nuclear egress of herpes simplex virus type 2 (HSV-2) capsids, function to promote nuclear egress, we examined how the lack of each protein impacted NEC localization. These analyses revealed a function of pUL16 in nuclear egress that is distinct from that of pUL21, uncovered a novel role for pUL21 in regulating NEC activity and shed new light on how a viral kinase, pUs3, regulates nuclear egress. Nuclear egress of viral capsids is a common feature of the replicative cycle of all herpesviruses. A complete understanding of all aspects of nuclear egress, including how viral NEC activity is controlled, may yield strategies to disrupt this process that could be applied to the development of herpes-specific antiviral drugs.
Client processing is altered by novel myopathy-causing mutations in the HSP40 J domain
Authors: Pullen Melanie Y. , Weihl Conrad C. , True Heather L. 
Published: February 2020

AbstractThe misfolding and aggregation of proteins is often implicated in the development and progression of degenerative diseases. Heat shock proteins (HSPs), such as the ubiquitously expressed Type II Hsp40 molecular chaperone, DNAJB6, assist in protein folding and disaggregation. Historically, mutations within the DNAJB6 G/F domain have been associated with Limb-Girdle Muscular Dystrophy type 1D, now referred to as LGMDD1, a dominantly inherited degenerative disease. Recently, novel mutations within the J domain of DNAJB6 have been reported in patients with LGMDD1. Since novel myopathy-causing mutations in the Hsp40 J domain have yet to be characterized and both the function of DNAJB6 in skeletal muscle and the clients of this chaperone are unknown, we set out to assess the effect of these mutations on chaperone function using the genetically tractable yeast system. The essential yeast Type II Hsp40, Sis1, is homologous to DNAJB6 and is involved in the propagation of yeast prions. Using phenotypic, biochemical, and functional assays we found that homologous mutations in the Sis1 J domain differentially alter the processing of specific yeast prion strains, as well as a non-prion substrate. These data suggest that the newly-identified mutations in the J domain of DNAJB6 cause aberrant chaperone function that leads to the pathogenesis in LGMDD1.
Optimum Threshold Minimizes Noise in Timing of Intracellular Events
Authors: Kannoly Sherin , Gao Tianhui , Dey Supravat , Wang Ing-Nang , Singh Abhyudai , Dennehy John J. 
Published: February 2020

ABSTRACTHow the noisy expression of regulatory proteins affects timing of intracellular events is an intriguing fundamental problem that influences diverse cellular processes. Here we use the bacteriophage λ to study event timing in individual cells where cell lysis is the result of expression and accumulation of a single protein (holin) in theEscherchia colicell membrane up to a critical threshold level. Site-directed mutagenesis of the holin gene was used to generate phage variants that vary in their timing of lysis from 30 to 190 min. Observation of the lysis times of single cells reveals an intriguing finding – the noise in lysis timing first decreases with increasing lysis time to reach a minimum, and then sharply increases at longer longer lysis times. A mathematical model with stochastic expression of holin together with dilution from cell growth was sufficient to explain the non-monotonic noise profile, and identify holin accumulation thresholds that generate precision in lysis timing.
A novel function of sphingosine kinase 2 in the metabolism of sphinga-4,14-diene lipids
Authors: Couttas Timothy A , Rustam Yepy H , Song Huitong , Qi Yanfei , Teo Jonathan D , Chen Jinbiao , Reid Gavin E , Don Anthony S 
Published: February 2020

AbstractThe number, position, and configuration of double bonds in lipid acyl chains affects membrane packing, fluidity, and recruitment of signalling proteins. Studies on mammalian sphingolipids have focused on those with a saturated sphinganine or mono-unsaturated sphingosine long chain base. Sphingolipids with a diunsaturated sphingadiene base have been reported but are poorly characterised. Employing high-resolution untargeted mass spectrometry, we observed marked accumulation of lipids containing a sphingadiene base, but not those with a more common sphingosine backbone, in the hippocampus of mice lacking the metabolic enzyme sphingosine kinase 2 (SphK2). Applying ultraviolet photodissociation tandem mass spectrometry (UVPD-MS/MS) the double bonds were confidently assigned to the C4-C5 and C14-C15 positions of the sphingoid base. Sphingosine kinases are involved in lysosomal catabolism of all sphingolipids, producing sphingoid base phosphates that are irreversibly degraded by sphingosine 1-phosphate lyase. Both SphK1 and SphK2 phosphorylated sphinga-4,14-diene as efficiently as sphingosine, however deuterated tracer experiments demonstrated that ceramides with a sphingosine base are more rapidly metabolised in cultured cells than those with a sphingadiene base. SphK2 silencing significantly impeded the catabolism of both sphingosine- and sphingadiene-based sphingolipids. Since SphK2 is the dominant sphingosine kinase in brain, we propose that accumulation of sphingadiene lipids in SphK2-deficient brains results from the intrinsically slower catabolism of sphingadiene lipids, combined with a bottleneck in the catabolic pathway created by the absence of SphK2. We speculate that accumulation of these lipids in the absence of SphK2 function may affect the fluidity and signalling properties of cell membranes.
Maternal arterial blood values during delivery: effect of mode of delivery, maternal characteristics, obstetric interventions and correlation to fetal umbilical cord blood
Authors: Zaigham Mehreen , Helfer Sara , Kristensen Karl Heby , Isberg Per-Erik , Wiberg Nana 
Published: February 2020

AbstractObjectiveTo determine a reference interval for maternal arterial blood values during vaginal delivery and to elucidate the effect of common maternal characteristics and obstetric interventions on maternal acid base values during vaginal and planned cesarean section (CS).DesignProspective, observational study of randomly selected women undergoing vaginal deliveries and planned CS at Skåne University Hospital, Malmö, Sweden.ResultsTwo hundred and fifty women undergoing vaginal delivery (VD) and fifty-eight women undergoing planned CS were recruited. We found significant differences for gestational age, parity, artery pH, pCO2, pO2, sO2and cord venous pH, pCO2and lactate between the two study groups (P< 0.005). For women undergoing vaginal delivery, we found significant changes in base deficit, hemoglobin, bilirubin, potassium, glucose and lactate values as compared to women with planned CS (P< 0.02). Maternal characteristics did not significantly affect acid base parameters however, multiple regression showed significant associations for the use of epidural anesthesia on maternal pH (P< 0.05) and pO2(P< 0.01); and synthetic oxytocin on pCO2(P= 0.08), glucose (P< 0.00) and lactate (P< 0.02) in maternal blood. Maternal arterial pH, pCO2and lactate correlated significantly to values in venous umbilical cord blood (P< 0.000).ConclusionsReference values for maternal arterial blood gases in vaginal deliveries for term pregnancies were outlined and we found that most arterial blood gas parameters varied significantly according to mode of delivery. The use of different obstetrical interventions like epidural anesthesia or synthetic oxytocin, resulted in significant changes in blood gas values.
Similarity between deviant peers: Developmental trends in influence and selection*
Authors: Ragan Daniel T. 
Published: February 2020

AbstractThe association between an adolescent's own behavior and that of his or her peers remains a key empirical finding in the study of delinquency, and this similarity is often explained in criminology by invoking processes of social influence and homophily. Adolescence is a period of rapid change for both individuals and their surroundings, however, and influence and homophily are often discussed without attending to their development over time. In the current study, I employ longitudinal social network models to estimate social influence and homophily related to alcohol and cigarette use and to determine whether there is change in the strength of these processes. Furthermore, I test whether the broader social environment conditions these processes and their observed changes. The results from this study indicate that although influence from peers decreases from early to mid‐adolescence, homophily on drinking and smoking increases. There is also evidence that school‐level opportunities and expectations affect social influence and homophily but do not account for the average changes observed in these processes.
genodive version 3.0: Easy‐to‐use software for the analysis of genetic data of diploids and polyploids
Authors: Meirmans Patrick G. 
Published: February 2020

Abstractgenodive version 3.0 is a user‐friendly program for the analysis of population genetic data. This version presents a major update from the previous version and now offers a wide spectrum of different types of analyses. genodive has an intuitive graphical user interface that allows direct manipulation of the data through transformation, imputation of missing data, and exclusion and inclusion of individuals, population and/or loci. Furthermore, genodive seamlessly supports 15 different file formats for importing or exporting data from or to other programs. One major feature of genodive is that it supports both diploid and polyploid data, up to octaploidy (2n = 8x) for some analyses, but up to hexadecaploidy (2n = 16x) for other analyses. The different types of analyses offered by genodive include multiple statistics for estimating population differentiation (φST, FST, FʹST, GST, GʹST, GʹʹST, Dest, RST, ρ), analysis of molecular variance‐based K‐means clustering, Hardy–Weinberg equilibrium, hybrid index, population assignment, clone assignment, Mantel test, Spatial Autocorrelation, 23 ways of calculating genetic distances, and both principal components and principal coordinates analyses. A unique feature of genodive is that it can also open data sets with nongenetic variables, for example environmental data or geographical coordinates that can be included in the analysis. In addition, genodive makes it possible to run several external programs (lfmm, structure, instruct and vegan) directly from its own user interface, avoiding the need for data reformatting and use of the command line. genodive is available for computers running Mac OS X 10.7 or higher and can be downloaded freely from: http://www.patrickmeirmans.com/software.
The preoperative platelet distribution width: A predictive factor of the prognosis in patients with non‐small cell lung cancer
Authors: Liu Chang , Zhang Hua , Qi Qi , Zhang Bin , Yue Dongsheng , Wang Changli 
Published: February 2020

AbstractBackgroundThe prognostic value of platelet distribution width (PDW) is different in various malignancies. The purpose of this study was to identify the relationship between preoperative PDW and survival in patients with non‐small cell lung cancer (NSCLC).MethodsOptimal cutoff values of PDW were confirmed using a receiver operating characteristic (ROC) curve. The Kaplan‐Meier method and log‐rank test were used to estimate disease‐free survival (DFS) and overall survival (OS). Univariate and multivariate Cox regression models were used for prognostic analysis. The likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare two models of the TNM staging system and the PDW‐TNM staging system (combination of PDW and the TNM staging system).ResultsSurvival analysis indicated that the disease‐free survival (DFS) and overall survival (OS) of patients with PDW > 12.65 were both significantly longer than those of patients with PDW ≤ 12.65. Multivariate analysis showed that PDW was an independent prognostic factor for DFS and OS. After the two prediction models were established, further LRT analysis showed that the PDW‐TNM model had a better ability to assess patient prognosis.ConclusionsPDW might act as an independent risk factor to predict progression and prognosis. Preoperative PDW combined with the TNM staging system showed a better ability to assess the prognosis of NSCLC patients.Key points
Our study focused on the prognostic value of preoperative PDW in 750 patients with NSCLC. We also analyzed preoperative PDW in different stages and histological subtypes systematically.
A model built by preoperative PDW combined with the TNM staging system had a better prognostic ability. LRT was used to calculate values of the goodness of fit between the model and the TNM staging system.
The safety and feasibility of intraoperative near‐infrared fluorescence imaging with indocyanine green in thoracoscopic sympathectomy for primary palmar hyperhidrosis
Authors: Pei Guotian , Liu Yanguo , Liu Qiang , Min Xianjun , Yang Yingshun , Wang Shuai , Liu Jun , Wang Jun , Huang Yuqing 
Published: February 2020

BackgroundWe investigated the safety and feasibility of intraoperative near‐infrared (NIR) imaging using indocyanine green (ICG) during sympathectomy in the management of primary palmar hyperhidrosis (PPH).MethodsWe performed a retrospective review of 142 patients (ICG group) who underwent endoscopic thoracic sympathectomy (ETS) between February 2018 and April 2019. All patients received a 5 mg/kg infusion of ICG 24 hours preoperatively. The vital signs before and after ICG injection and adverse reactions were recorded. Meanwhile, 498 patients (Non‐ICG group) who underwent ETS by normal thoracoscopy during August 2017 to April 2019 were also reviewed to compare the abnormal white blood cell (WBC) counts, alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine (Cr) levels before and after operation between two groups.ResultsFor ICG group, the vital signs including body temperature, heart rate and blood pressure before and after ICG injection were stable. There was no significant difference in the abnormal WBC counts, ALT, AST, BUN, and Cr levels before and after operation between two groups. Only one patient had mild adverse reaction (0.7%) after ICG injection. The visibility rate of all sympathetic ganglions was 96.7% (1369/1415). The visibility rate from T1 to T5 was 98.23% (278/283), 98.23% (278/283), 97.17% (275/283), 95.76% (271/283), and 94.35% (267/283), respectively. There was no significant difference in the visibility rate with regard to age, gender, height, weight, body mass index, and PPH grade.ConclusionsNIR fluorescence imaging with ICG for identifying sympathetic ganglions is relatively safe and feasible.Key points• Significant findings of the study.NIR fluorescence imaging with ICG for identifying sympathetic ganglions is relatively safe and feasible.• What this study adds.This technology may take the place of the rib‐oriented method as standard practice for the precise localization of sympathetic ganglions, and may improve the effect of sympathectomies.
Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC
Authors: Ishii Hidenobu , Azuma Koichi , Kawahara Akihiko , Kinoshita Takashi , Matsuo Norikazu , Naito Yoshiko , Tokito Takaaki , Yamada Kazuhiko , Akiba Jun , Hoshino Tomoaki 
Published: February 2020

BackgroundCD73 induces the dephosphorylation of adenosine monophosphate converting it to adenosine, enabling malignancies to escape from immune surveillance. Although CD73 overexpression has been reported to be a poor prognostic factor in several malignancies including non‐small cell lung cancer (NSCLC), its predictive relevance in NSCLC patients receiving immune checkpoint inhibitors is unknown. The present research was conducted to investigate the prognostic significance of CD73 expression in NSCLC patients receiving immune checkpoint inhibitors (ICIs).MethodsWe screened 91 patients with advanced or recurrent NSCLC who received immune checkpoint inhibitors. CD73 expression was evaluated immunohistochemically using tissue specimens obtained just before treatment with ICIs.ResultsAnalysis of progression‐free survival (PFS) and overall survival (OS) in relation to several levels of CD73 expression (1%, 10%, 30%, and 50%) showed that both tended to be more favorable as expression of CD73 increased. PFS and OS were longer for patients in whom at least 50% of the tumor cells expressed CD73 than for those in whom <50% of the tumor cells did so. In patients who were positive for EGFR mutation, immune checkpoint inhibitors were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC. Furthermore, CD73 expression was predictive factor for the PFS independent of PD‐L1 expression in patients with EGFR mutation.ConclusionsHigh CD73 expression may predict a favorable response to ICIs in NSCLC patients, especially those harboring EGFR mutations.Key pointsSignificant findings of the study: In patients who were positive for EGFR mutation, immune checkpoint inhibitors (ICIs) were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC.What this study adds: High CD73 expression may predict a favorable response to immune checkpoint inhibitors in NSCLC patients, especially those harboring EGFR mutations.
Cone‐beam CT radiomics features might improve the prediction of lung toxicity after SBRT in stage I NSCLC patients
Authors: Qin Qingjin , Shi Anhui , Zhang Ran , Wen Qiang , Niu Tianye , Chen Jinhu , Qiu Qingtao , Wan Yidong , Sun Xiaorong , Xing Ligang 
Published: February 2020

AbstractBackgroundStereotactic body radiotherapy (SBRT) is the standard care for inoperable early stage non‐small cell lung cancer (NSCLC). The purpose of our study was to investigate whether a prediction model based on cone‐beam CT (CBCT) plus pretreatment CT radiomics features could improve the prediction of tumor control and lung toxicity after SBRT in comparison to a model based on pretreatment CT radiomics features alone.MethodsA total of 34 cases of stage I NSCLC patients who received SBRT were included in the study. The pretreatment planning CT and serial CBCT radiomics features were analyzed using the imaging biomarker explorer (IBEX) software platform. Multivariate logistic regression was conducted for the association between progression‐free survival (PFS), lung toxicity and features. The predictive capabilities of the models based on CBCT and CT features were compared using receiver operating characteristic (ROC) curves.ResultsFive CBCT features and two planning CT features were correlated with disease progression. Six CBCT features and two planning CT features were related to lung injury. The ROC curves indicated that the model based on the CBCT plus planning CT features might be better than the model based on the planning CT features in predicting lung injury. The other ROC curves indicated that the model based on the planning CT features was similar to the model based on the CBCT plus planning CT features in predicting disease progression.ConclusionsBoth pretreatment CT and CBCT radiomics features could predict disease progression and lung injury. A model with CBCT plus pretreatment CT radiomics features might improve the prediction of lung toxicity in comparison with a model with pretreatment CT features alone.Key points

Significant findings of the study: A model with cone‐beam CT radiomics features plus pre‐treatment CT radiomics features might improve the prediction of lung toxicity after SBRT in stage I NSCLC patients.

What this study adds: In the prediction of PFS and lung toxicity in early‐stage NSCLC patients treated with SBRT, CBCT radiomics could be another effective method.