bluuebunny/crossref_metadata_2025 huggingface dataset:
Gap junctions coordinate the propagation of glycogenolysis induced by norepinephrine in the pineal gland
Authors: Eugenin Eliseo A. , Valdebenito Silvana , Gorska Anna Maria , Martínez Agustin D. , Bitran Marcela , Sáez Juan C.
Published: August 2019

Chemical and electrical synapses are the two major communication systems that permit cell‐to‐cell communication within the nervous system. Although most studies are focused on chemical synapses (glutamate, γ‐aminobutyric acid, and other neurotransmitters), clearly both types of synapses interact and cooperate to allow the coordination of several cell functions within the nervous system. The pineal gland has limited independent axonal innervation and not every cell has access to nerve terminals. Thus, additional communication systems, such as gap junctions, have been postulated to coordinate metabolism and signaling. Using acutely isolated glands and dissociated cells, we found that gap junctions spread glycogenolytic signals from cells containing adrenoreceptors to the entire gland lacking these receptors. Our data using glycogen and lactate quantification, electrical stimulation, and high‐performance liquid chromatography with electrochemical detection, demonstrate that gap junctional communication between cells of the rat pineal gland allows cell‐to‐cell propagation of norepinephrine‐induced signal that promotes glycogenolysis throughout the entire gland. Thus, the interplay of both synapses is essential for coordinating glycogen metabolism and lactate production in the pineal gland.

image
A rat model of placental inflammation explains the unexplained elevated maternal serum alpha‐fetoprotein associated with adverse pregnancy outcomes
Authors: Hu Jilin , Zhang Jinman , Chan Ying , Zhu Baosheng
Published: August 2019

Aim

It has been reported in numerous studies that elevated maternal serum alpha‐fetoprotein (MS‐AFP) is associated with adverse pregnancy outcomes (APO), such as pre‐eclampsia, stillbirth, preterm birth and fetal growth restriction. However, the mechanism linking elevated MS‐AFP and APO is obscure. In this study, we tried to explore the mechanism by using pregnant rats.

Methods

Lipopolysaccharide (LPS) was used to induce placental inflammation in pregnant rats. Maternal serum and placental inflammatory cytokines and placental morphology were used to assess the level of placental inflammation. The incidences of APO and the levels of MS‐AFP were evaluated. The expressions of alpha‐fetoprotein (AFP) in the related organs and fetal serum AFP levels were detected.

Results

Compared to saline‐treated pregnant rats, LPS led to elevated maternal serum and placental inflammatory cytokines and a higher rate of placental inflammation. Lipopolysaccharide resulted in the features of APO and at the same time elevated MS‐AFP. Maternal serum alpha‐fetoprotein levels were significantly correlated to the evaluation parameters of APO. Lipopolysaccharide did not increase the expressions of AFP in fetal liver, maternal liver and placenta, but reduced the fetal serum AFP levels.

Conclusion

The phenomenon that elevated MS‐AFP is associated with APO, which has been reported in human pregnancies, is observed in our rat model. Placental inflammation can be the potential cause linking the two manifestations together. Although the source of elevated MS‐AFP is not identified, fetal blood circulation is suspected. Our study may provide an animal model for the future studies on this subject.
Response: How Do We Know What We Know About the Amish and Other Minorities?
Authors: Kraybill Donald B.
Published: August 2019

The appraisal by Cory Anderson, Joseph Donnermeyer, Jeffrey Longhofer, and Steven Reschly (hereafter, appraisers) highlights a methodological divide that is important to the study of the Amish and other ethnic or religious minorities. In my reply, I discuss how my work is rooted in a cultural analytic paradigm that differs from the appraisers’ methodological orientation. My reply includes a deconstruction of the appraisal and a discussion of its “shortcomings.” I conclude by showing how the discourse surrounding this appraisal raises important epistemological questions of how we understand human societies.
Predictors of sustained functional cure in hepatitis B envelope antigen‐negative patients achieving hepatitis B surface antigen seroclearance with interferon‐alpha–based therapy
Authors: Li Ming‐Hui , Yi Wei , Zhang Lu , Lu Yao , Lu Hui‐Hui , Shen Ge , Wu Shu‐Ling , Hao Hong‐Xiao , Gao Yuan‐Jiao , Chang Min , Liu Ru‐Yu , Hu Lei‐Ping , Cao Wei‐Hua , Chen Qi‐Qi , Li Jun‐Nan , Wan Gang , Xie Yao
Published: August 2019

Hepatitis B surface antigen (HBsAg) loss is considered a functional cure in chronic hepatitis B (CHB). However, the durability of HBsAg loss after stopping treatment remains unknown. This study aimed to assess the sustained functional cure achieved by interferon therapy in hepatitis B envelope antigen (HBeAg)‐negative CHB patients. In this prospective study, 176 HBeAg‐negative CHB patients with functional cure were enrolled for 12 weeks of cessation treatment, and treatment information and baseline data were collected. Hepatitis B virus (HBV) biomarkers and clinical biochemical indicators were evaluated every 3 months; liver imaging examinations were performed every 3‐6 months during the 48‐week follow‐up. The sustained functional cure was evaluated. After the 48‐week follow‐up, the sustained functional cure rate was 86.63%. The cumulative rates of HBsAg reversion and HBV DNA reversion were 12.79% and 2.33%, respectively. Consolidation treatment ≥ 12 weeks after HBsAg loss achieved a significantly higher rate of sustained functional cure and significantly lower rate of HBsAg reversion than consolidation treatment < 12 weeks (76.19% vs 90.00%, P = 0.022 and 23.81% vs 9.23%, P = 0.014, respectively). Patients with hepatitis B surface antibody (HBsAb) had higher rate of sustained functional cure than patients achieving HBsAg loss but without HBsAb (89.86% vs 73.53%, P = 0.012). Consolidation treatment ≥ 12 weeks (odds ratio [OR] 16.478; 95% confidence interval [CI], 2.135‐127.151; P = 0.007) and high HBsAb levels (OR 8.312; 95% CI, 1.824‐37.881; P = 0.006) were independent predictors of sustained functional cure. Results suggested that 12 weeks of consolidation therapy after HBsAg clearance and elevated HBsAb levels help to improve functional cure.
Long‐term efficacy and safety of peginterferon in the treatment of children with HBeAg‐positive chronic hepatitis B
Authors: Liu Yunhua , Li Hui , Yan Xiaohui , Wei Jia
Published: August 2019

Achieving ‘clinical cure’ in children with chronic hepatitis B (CHB) with safe and effective antiviral treatment is an unmet medical need. Peginterferon (PegIFN) has higher hepatitis B s antigen (HBsAg) clearance than nucleoside analogs (NUC). Currently, studies on interferon (IFN) in the treatment of Chinese children with CHB are relatively rare. This study aimed to further explore the efficacy of PegIFNα‐2a as an antiviral treatment in Chinese children and analyse the long‐term follow‐up after drug discontinuation. We enrolled 118 patients with CHB (2‐16 years old, 79 cases are males) treated with PegIFNα‐2a by the author in the Third People's Hospital of Kunming City from February 2009 to February 2015. The course of treatment was 52 weeks, with a follow‐up period of 104 weeks. All the patients completed at least 1 dose, of which 104 completed at least 36 weeks of treatment and 104 weeks of follow‐up. During treatment and follow‐up, indicators such as alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA and HBV serological markers were monitored, and the efficacy and safety of PegIFNα‐2a in the treatment of CHB patients were observed. Hepatitis B e antigen (HBeAg) clearance and seroconversion rates were 53.8% and 49%, respectively, when the drug was discontinued; 72.1% and 72.1%, respectively, at the end of the follow‐up; and 98.2% and 98%, respectively, for sustained response. HBsAg clearance and seroconversion rates were 48.1% and 47.1%, respectively, when the drug was discontinued; 53.8% and 52.9%, respectively, at the end of the follow‐up; and 94% and 95.9%, respectively, for sustained response. The HBV DNA suppression rate was 89.4% when the drug was discontinued, 90.4% at the end of the follow‐up and 97.8% for sustained response. Two patients had virological relapse (2.3%) during follow‐up; however, no clinical relapse occurred. Multivariate regression analysis showed that genotype B, weight < 25 kg or between 25 and 45 kg, and reduction of HBsAg by more than 1 log following 24 weeks of treatment were independent predictors of HBsAg clearance at the end of follow‐up. Adverse events that occurred during treatment were similar to those reported in previous clinical studies on PegIFN. The results of this study showed that PegIFN was safe and effective in the treatment of children with CHB, and sustained response could be achieved after treatment. PegIFN treatment of children with CHB helps more achieve ‘clinical cure’.
Long‐term consequences of stopping HBIG and/or nucleotide analogues in liver transplant recipients administered hepatitis B vaccination to prevent HBV reinfection
Authors: Duan Bin‐Wei , Tian Lan‐Tian , Lin Dong‐Dong , Zhang Jing , Guo Qing‐Liang , Wu Ju‐Shan , Zeng Dao‐Bing , Lu Shi‐Chun
Published: August 2019

Background

The long‐term administration of nucleotide analogues (NAs) and hepatitis B immune globulin (HBIG) comprises standard prophylaxis for patients with hepatitis B virus (HBV)‐related liver diseases to prevent HBV reinfection after liver transplantation (LT). However, prolonging the prophylaxis strategy involves safety issues, such as the development of escape mutations and/or emerging resistant strains, and is also associated with high costs; further, it remains unclear how long prophylactic treatment should be continued.

Method

Liver transplantation recipients responding to hepatitis B vaccination due to HBV‐related liver diseases were retrospectively analysed after stopping HBIG and/or NAs, administered to prevent HBV reinfection, after long‐term follow‐up. The safety and effectiveness of the strategy were then evaluated for these responders.

Result

Seventy‐eight responders were enrolled. All responders discontinued HBIG, among which 36 stopped both HBIG and NAs. During follow‐up, four recipients experienced HBV reinfection, which was associated with HBV escape mutations, after the withdrawal of both HBIG and NAs. No death or graft loss occurred in recipients during the follow‐up period.

Conclusion

A careful withdrawal of HBIG and/or NAs is feasible and safe for responders to hepatitis B vaccination receiving transplants for HBV‐related liver diseases.
Modelling the survival of Listeria monocytogenes strains in soft lactic cheese following acid and salt stress exposures
Authors: Sibanda T. , Buys E.M.
Published: August 2019

This study evaluated the survival responses of Listeria monocytogenes strains (individually and mixed) in a soft lactic cheese following acid and salt stress exposures. The Weibull and log-linear with tail models were used to predict the survival responses of the pathogen in the cheese stored at 4°C for 15 days. Both models showed a good prediction accuracy for stressed L. monocytogenes cells (Af = 1·00) and higher prediction errors (Af = 1·12−1·14) for nonstressed cells. The inactivation rates (δ (d) and kmax (d−1)) were significantly lower (P < 0·05) for cells subjected to stress exposure indicating the enhanced tolerance to food stress. However, while enhanced tolerance appeared to be the main effect of stress pre-exposure, in one susceptible strain (69), stress exposure led to higher rates of inactivation. When introduced into the food as mixed strains, one strain out-lived others and remained as the sole survivor. Such strains that perhaps have a predilection for the food environment can provide more cautious estimates of kinetic parameters for predicting L. monocytogenes responses in foods especially if their stress-hardened tolerant cells are used.

Significance and Impact of the Study

The ability to predict the growth and survival of Listeria monocytogenes in contaminated RTE foods is essential for listeriosis risk assessment. The results of this study provided valuable information on the kinetic parameters of survival of some L. monocytogenes strains found within the South African food environment. In addition to showing differences in the survival responses among strains, the study also showed the importance of the pre-contamination state of the cells in influencing survival kinetics.
Conveying emphasis for intensity: Lexical and syntactic strategies
Authors: Beltrama Andrea , Trotzke Andreas
Published: August 2019

Emphasis is a widely investigated notion in linguistics. In this article, we focus on emphasis for intensity, a general linguistic strategy whereby linguistic objects are given prominence by virtue of being selected from the upper range of a scale. We consider two linguistic domains where emphasis for intensity can be observed: the lexical domain, where it is conveyed via a variety of intensifiers, and the domain of syntax, where it can be conveyed via different types of non‐canonical word order. While distinct in many respects, such families of constructions can be seen as conveying a unified effect, raising a number of issues concerning how the relation between emphasis and scalarity is best captured across languages and constructions.
What is the most plausible account of the role of parafoveal processing in reading?
Authors: Andrews Sally , Veldre Aaron
Published: August 2019

Online reading requires exquisitely precise coordination of the oculomotor processes involved in extracting and integrating information from both the word currently fixated in foveal vision and upcoming words in the parafovea. Parafoveal preview effects, assessed using the gaze‐contingent boundary paradigm, provide a rich source of evidence about the extent and depth of processing conducted on upcoming parafoveal words and how it contributes to reading. This review focuses on recent demonstrations of plausibility preview effects which provide strong evidence that readers extract semantic information from parafoveal words and that newly identified words are rapidly and incrementally integrated with the developing representation of the sentence to generate graded predictions about potential plausible continuations. Individual differences in the quality of skilled readers' lexical representations, indexed by the combination of reading and spelling ability, determine how semantic and contextual information extracted from parafoveal words influences oculomotor control. This evidence has important implications for theories of eye‐movement control in online reading.
An acoustic perspective on 45 years of infant speech perception, Part 1: Consonants
Authors: Narayan Chandan R.
Published: August 2019

In this two‐part review, we examine major results from infant consonant (Part 1), vowel, and suprasegmental (Part 2) discrimination research over the past 45 years from an acoustic perspective—an exegesis of the developmental speech perception literature that appeals to both acoustic aspects of speech contrasts and historically relevant typological facts about the sound systems of the world's languages. We argue that infants' speech discrimination abilities are best viewed through a lens that considers both synchronic and diachronic aspects of the particular speech contrast. The key to this approach is the notion that acoustic–perceptual salience, or the relative separation of speech categories along perceptually relevant acoustic dimensions and corresponding discrimination performance in adults, is reflected in both infants perceptual performance and patterns observed in phonological typology and history. The review highlights challenges presented by four decades of literature, identifies broad patterns in infant consonant perception according to the acoustic properties of speech contrasts, and offers linguistically motivated explanations and directions for future research into the nature of young infants' discrimination abilities.
Identity, displacement and destiny
Authors: Emden Joshua , Ellams Inua
Published: August 2019

The poet, playwright, performer and artist reflects on the role of his work in multicultural Britain
The impact of uncorrected astigmatism on night driving performance
Authors: Black Alex A , Wood Joanne M , Colorado Luisa H , Collins Michael J
Published: August 2019

Purpose

To investigate the effect of uncorrected astigmatism on night driving performance on a closed‐road circuit.

Methods

Participants included 10 drivers (mean age 24.4 ± 7.0 years), with low to moderate bilateral astigmatism (0.75–1.50 DC), who were regular contact lens (CL) wearers. Vision and night driving performance were assessed in a cross‐over design with a toric CL and a best‐sphere spherical CL. Binocular visual function measures included photopic and mesopic visual acuity (VA), contrast sensitivity (CS), mesopic motion sensitivity and glare tests (Mesotest® II and Halometer). Night‐time driving performance was assessed on a closed‐road circuit, which included measures of sign recognition, hazard detection and avoidance, pedestrian recognition distances, lane keeping, speed and overall driving score.

Results

Correction of astigmatism with toric CL significantly improved mesopic VA, photopic and mesopic CS, mesopic motion sensitivity, and reduced glare (p < 0.05), compared to the spherical CL; there were no significant effects of visual correction type on photopic VA. Correction of astigmatism using toric CL resulted in significant improvements in night driving performance, compared to driving with spherical CL, particularly for sign recognition, avoidance of low contrast hazards, increased pedestrian recognition distances and overall driving score (p < 0.05).

Conclusions

Correction of low to moderate levels of astigmatism had significant positive effects on night‐time driving performance and related tests of visual performance. This has important implications for optical corrections to improve night road safety of drivers with astigmatism.
An update on allergy and anaphylaxis in pediatric anesthesia
Authors: Stepanovic Bojana , Sommerfield David , Lucas Michaela , von Ungern‐Sternberg Britta S.
Published: August 2019

Childhood allergy is common, and increasing. Many children are incorrectly labeled as having allergy or adverse drug reactions. This can pose a dilemma for anesthetists and lead to a change in practice or drug selection. We review the pathophysiology of hypersensitivity reactions and the implications for anesthesia of food allergy, atopy, and family history of allergy in children. The epidemiology of anaphylaxis is discussed. We discuss the common triggers of perioperative anaphylaxis in children and explore emerging triggers including chlorhexidine and sugammadex. Accurate data on pediatric perioperative anaphylaxis is limited worldwide, with marked geographic variation. This highlights the need for accurate local, district and/or nationwide incident reporting. The clinical features, diagnosis, and management of anaphylaxis under anesthesia are discussed. We review the process of expert allergy testing following a suspected case of anaphylaxis to guide future safe anesthesia administration. The preoperative consultation is an opportunity for referral for allergy testing to allow de‐labeling. This has the potential for improved antibiotic stewardship and more effective treatment with first‐line therapeutic agents.
Effects of recipient oocyte source, number of transferred embryos and season on somatic cell nuclear transfer efficiency in sheep
Authors: Yuan Yixin , Liu Ruming , Zhang Xiaosheng , Zhang Jinlong , Zheng Zi , Huang Chengjun , Cao Guifang , Liu Haijun , Zhang Xianfu
Published: August 2019

To improve the efficiency of somatic cell nuclear transfer (SCNT) in sheep, we investigated the effects of recipient oocyte source, number of transferred embryos and season on the pregnancy and live lamb rates for sheep somatic cell nuclear transfer embryos. Follicle‐stimulating hormone (FSH)‐stimulated ovaries produced significantly more oocytes both in total and of suitable quality for maturation culture than those without FSH treatment (from slaughterhouse). However, their in vitro maturation rates were similar. Embryos were reconstructed using adult fibroblast cells into enucleated MII oocytes. The pregnancy and term rates were significantly higher in the FSH‐stimulated group than in the slaughterhouse one. Oocytes from FSH‐stimulated ovaries were enucleated as recipient cytoplasm for nuclear transfer in the following experiments. The transfer of 7–9 and 11–13 embryos produced significantly higher pregnancy rates than that of six embryos. However, the former groups exhibited similar live lamb rates. FSH‐stimulated ovaries produced significantly more oocytes in November and December (winter) than in May to July (summer), but the associated maturation rate did not increase. Pregnancy and term rates were significantly higher when transfer occurred in winter than in summer. In conclusion, FSH treatment produced significant benefit regarding the number and quality of collected oocytes and also for the pregnancy and live lamb rates for reconstructed embryos. However, the transfer of an appropriate number of embryos (7–13) and at an appropriate season (winter) increased pregnancy and term rates.
Population source affects competitive response and effect in a C4 grass (Panicum virgatum)
Authors: Flint Shelby A. , Olofson Dana , Jordan Nicholas R. , Shaw Ruth G.
Published: August 2019

Grassland restoration success depends on the development of plant communities that accord with restoration goals. Intraspecific variation in competitiveness may affect community development. For some grassland species, germplasm can be obtained from sources ranging from wild collections to selectively bred cultivars. The extent to which population source affects competitive outcomes in restoration projects is unclear. We addressed this knowledge gap in a glasshouse experiment comparing competitive response and effect among three sources of switchgrass (Panicum virgatum) that are available for restoration: selectively bred cultivars, commercial ecotypes (commercially produced but not deliberately selected), and wild collections. Two strains per source type were grown with four associates chosen to encompass varied functional groups: conspecifics, Bromus inermis, Cirsium arvense, and Solanum ptycanthum. Switchgrass competitive response was evaluated for survival, height, biomass, and shoot:root biomass ratio; competitive effect was assessed as associate survival, height, biomass, and shoot:root ratio. Competitive responses of cultivars and commercial ecotypes were broadly similar, although cultivar biomass exceeded both that of ecotypes and wild collections, and ecotypes had the highest shoot:root ratio. Wild collections were most negatively affected by competition. The shoot:root ratios of all sources were highest when grown with S. ptycanthum, indicating that competitive responses were plastic; plasticity in fitness‐related traits can contribute to persistence in variable environments. Cultivars exerted negative effects on B. inermis. Secondary analyses indicated that all switchgrass sources were most inhibited by the annual S. ptycanthum. To summarize, population source affected multiple aspects of switchgrass competitive ability, when grown against functionally varied associates.
The HLA‐DRB1*14:208 allele detected in a Taiwanese individual
Authors: Yang Kuo‐Liang , Lin Py‐Yu
Published: August 2019

Nucleotide substitutions in exons 2 and 3 of HLA‐DRB1*14:07:01 result in a new allele, HLA‐DRB1*14:208.
Safety and efficacy of Option B+ ART in Malawi: few severe maternal toxicity events or infant HIV infections among pregnant women initiating tenofovir/lamivudine/efavirenz
Authors: Harrington Bryna J. , DiPrete Bethany L. , Jumbe Allan N. , Ngongondo McNeil , Limarzi Laura , Wallie Shaphil D. , Chagomerana Maganizo B. , Hosseinipour Mina C. ,   the S4 Study Team
Published: August 2019

Objectives

Malawi's Option B+ universal antiretroviral therapy (ART) program for pregnant and breastfeeding women does not include routine laboratory monitoring. We report safety outcomes of pregnant women who initiated ART through Option B+.

Methods

We analysed 12‐month data from an observational cohort study on Option B+ among women newly initiating tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) at a government antenatal clinic in Lilongwe, Malawi. Proportions of women engaged in care, incidence of DAIDS grade ≥ 2 laboratory toxicity, grade ≥ 3 adverse events (AEs), viral suppression (<1000 copies/mL), birth outcomes and infant HIV infections are reported.

Results

At ART initiation, participants (n = 299) had a median age of 26 years (IQR 22–30), median CD4 count of 352 cells/μl (IQR 231–520) and 94% were in WHO Stage 1. We noted 76 incident DAIDS Grade ≥ 2 laboratory results among 58 women, most commonly elevated liver function tests (n = 30 events) and low haemoglobin (n = 27). No women had elevated creatinine. Clinical AEs (n = 45) were predominantly infectious diseases and Grade 3. Five participants (2%) discontinued TDF/3TC/EFV due to virologic failure (3) or toxicity (2). Twelve months after ART initiation, most women were engaged in care (89%) and had HIV RNA < 1000 copies/ml (90%). 8% of pregnancies resulted in preterm birth, 9% were low birthweight (<2500 g), and 2% resulted in infant HIV infection at 6 weeks post‐delivery.

Conclusion

Most women remained on ART and were virally suppressed 12 months after starting Option B+. Few infants contracted HIV perinatally. While some women experienced adverse laboratory events, clinical symptom monitoring is likely reasonable.
In planta gene targeting can be enhanced by the use of CRISPR/Cas12a
Authors: Wolter Felix , Puchta Holger
Published: August 2019

The controlled change of plant genomes by homologous recombination (HR) is still difficult to achieve. We previously developed the in planta gene targeting (ipGT) technology which depends on the simultaneous activation of the target locus by a double‐strand break and the excision of the target vector. Whereas the use of SpCas9 resulted in low ipGT frequencies in Arabidopsis, we were recently able to improve the efficiency by using egg cell‐specific expression of the potent but less broadly applicable SaCas9 nuclease. In this study, we now tested whether we could improve ipGT further, by either performing it in cells with enhanced intrachromosomal HR efficiencies or by the use of Cas12a, a different kind of CRISPR/Cas nuclease with an alternative cutting mechanism. We could show before that plants possess three kinds of DNA ATPase complexes, which all lead to instabilities of homologous genomic repeats if lost by mutation. As these proteins act in independent pathways, we tested ipGT in double mutants in which intrachromosomal HR is enhanced 20–80‐fold. However, we were not able to obtain higher ipGT frequencies, indicating that mechanisms for gene targeting (GT) and chromosomal repeat‐induced HR differ. However, using LbCas12a, the GT frequencies were higher than with SaCas9, despite a lower non‐homologous end‐joining (NHEJ) induction efficiency, demonstrating the particular suitability of Cas12a to induce HR. As SaCas9 has substantial restrictions due to its longer GC rich PAM sequence, the use of LbCas12a with its AT‐rich PAM broadens the range of ipGT drastically, particularly when targeting in CG‐deserts like promoters and introns.
Misidentifications of Echinochloa crus‐galli var. formosensis as Echinochloa oryzicola as a result of similar cpDNA sequences
Authors: Yasuda Kentaro , Nakayama Yuichiro
Published: August 2019

Echinochloa crus‐galli (L.) Beauv. var. formosensis Ohwi (2n = 6x = 54, AABBCC genomes) and Echinochloa oryzicola (Vasinger) Vasinger (2n = 4x = 36, AABB) are major paddy weeds in East and Southeast Asia. E. oryzicola has been generally considered to be a paternal genome donor of E. crus‐galli s. l., which includes E. crus‐galli var. formosensis based on cpDNA sequences. Thus, molecular characterization using polymerase chain reaction‐restriction fragment length polymorphism analysis of cpDNA has been proposed as a reliable method for discriminating between the two species. In this study, we report that four accessions of E. crus‐galli var. formosensis from Okinawa, Nagasaki, Shizuoka and Tokyo had similar cpDNA sequences to E. oryzicola and had been misidentified as E. oryzicola using molecular methods. In addition, our results demonstrated that these accessions likely inherited their chloroplast genomes from E. oryzicola and not from an anonymous diploid species during polyploidization. Our findings provide new insights into the evolution of E. crus‐galli s. l. and suggest that identification using the cpDNA molecular method alone is not an appropriate approach to differentiate E. crus‐galli var. formosensis and E. oryzicola.
A Comparison of the Physiology of Sedentary Behavior and Light Physical Activity in Adults With and Without a Physical Disability
Authors: Balemans Astrid C.J. , Houdijk Han , Koelewijn Gilbert R. , Piek Marjolein , Tubbing Frank , Visser-Meily Anne , Verschuren Olaf
Published: August 2019

Background: It is questionable whether postures that are regarded as sedentary behavior in able-bodied persons evoke comparable physiological responses in adults with stroke or cerebral palsy (CP). This study aimed to compare metabolic demand and muscle activity in healthy controls, adults with stroke, and adults with CP during sedentary behavior and light physical activities. Methods: Seventy-one adults (45.6 [18.9] y, range 18–86) participated in this study, of which there were 18 controls, 31 with stroke, and 22 with CP. The metabolic equivalent of task (MET) and level of muscle activation were assessed for different sedentary positions (sitting supported and unsupported) and light physical activities (standing and walking). Results: During sitting supported and unsupported, people with mild to moderate stroke and CP show comparable MET and electromyographic values as controls. While sitting unsupported, people with severe stroke show higher METs and electromyographic values (P < .001), and people with severe CP only show higher METs compared with controls (P < .05) but all below 1.5 METs. Standing increased electromyographic values in people with severe stroke or CP (P < .001) and reached values above 1.5 METs. Conclusions: Physiologic responses during sedentary behavior are comparable for controls and adults with mild to moderate stroke and CP, whereas higher metabolic demands and muscle activity (stroke only) were observed in severely affected individuals.
Challenging Antimicrobial Susceptibility and Evolution of Resistance (OXA-681) during Treatment of a Long-Term Nosocomial Infection Caused by a Pseudomonas aeruginosa ST175 Clone
Authors: Arca-Suárez Jorge , Fraile-Ribot Pablo , Vázquez-Ucha Juan Carlos , Cabot Gabriel , Martínez-Guitián Marta , Lence Emilio , González-Bello Concepción , Beceiro Alejandro , Rodríguez-Iglesias Manuel , Galán-Sánchez Fátima , Bou Germán , Oliver Antonio
Published: August 2019

Selection of extended-spectrum mutations in narrow-spectrum oxacillinases (e.g., OXA-2 and OXA-10) is an emerging mechanism for development of
in vivo
resistance to ceftolozane-tazobactam and ceftazidime-avibactam in
Pseudomonas aeruginosa
. Detection of these challenging enzymes therefore seems essential to prevent clinical failure, but the complex phenotypic plasticity exhibited by this species may often lead to their underestimation.
Emerging Terbinafine Resistance in
Trichophyton
: Clinical Characteristics, Squalene Epoxidase Gene Mutations, and a Reliable EUCAST Method for Detection
Authors: Saunte Ditte M. L. , Hare Rasmus K. , Jørgensen Karin M. , Jørgensen René , Deleuran Mette , Zachariae Claus O. , Thomsen Simon F. , Bjørnskov-Halkier Lars , Kofoed Kristian , Arendrup Maiken C.
Published: August 2019

In recent years, cases involving terbinafine-resistant
Trichophyton
isolates have been reported increasingly, particularly in India. We present 14 cases of terbinafine treatment failure in
Trichophyton
-infected Danish patients due to acquired resistance. Patients infected with
Trichophyton rubrum
(
n
 = 12) or
Trichophyton interdigitale
(
n
 = 2) with elevated terbinafine MICs during 2013–2018 were included.
Impact of the Major Candida glabrata Triazole Resistance Determinants on the Activity of the Novel Investigational Tetrazoles VT-1598 and VT-1161
Authors: Nishimoto Andrew T. , Whaley Sarah G. , Wiederhold Nathan P. , Zhang Qing , Yates Christopher M. , Hoekstra William J. , Schotzinger Robert J. , Garvey Edward P. , Rogers P. David
Published: August 2019

VT-1161 and VT-1598 are promising investigational tetrazole antifungals that have shown
in vitro
and
in vivo
activity against
Candida
and other fungi.
Candida glabrata
is a problematic opportunistic pathogen that is associated with high mortality in invasive infection, as well as both intrinsic and rapidly acquired antifungal resistance.
Independent Evolution with the Gene Flux Originating from Multiple
Xanthomonas
Species Explains Genomic Heterogeneity in Xanthomonas perforans
Authors: Newberry E. A. , Bhandari R. , Minsavage G. V. , Timilsina S. , Jibrin M. O. , Kemble J. , Sikora E. J. , Jones J. B. , Potnis N.
Published: August 2019

Bacterial leaf spot of tomato and pepper is an endemic plant disease with a global distribution. In this study, we investigated the evolutionary processes leading to the emergence of novel
X. perforans
lineages identified in Alabama. While one lineage was isolated from symptomatic tomato and pepper plants, confirming the host range expansion of
X. perforans
, the other lineage was isolated from tomato and acquired a novel transcription activation-like effector, here designated PthXp1. Functional analysis of PthXp1 indicated that it does not induce
Bs4
-mediated resistance in tomato and contributes to virulence, providing an adaptive advantage to strains on tomato. Our findings also show that different phylogenetic groups of the pathogen have experienced independent recombination events originating from multiple
Xanthomonas
species. This suggests a continuous gene flux between related xanthomonads associated with diverse plant hosts that results in the emergence of novel pathogen lineages and associated phenotypes, including host range.
Multi-omics Analyses Reveal Synergistic Carbohydrate Metabolism in Streptococcus mutans-Candida albicans Mixed-Species Biofilms
Authors: Ellepola K. , Truong T. , Liu Y. , Lin Q. , Lim T. K. , Lee Y. M. , Cao T. , Koo H. , Seneviratne C. J.
Published: August 2019

Candida albicans
, a major opportunistic fungal pathogen, is frequently found together with
Streptococcus mutans
in dental biofilms associated with severe childhood caries (tooth decay), a prevalent pediatric oral disease. However, the impact of this cross-kingdom relationship on
C. albicans
remains largely uncharacterized. Here, we employed a novel quantitative proteomics approach in conjunction with transcriptomic profiling to unravel molecular pathways of
C. albicans
when cocultured with
S. mutans
in mixed biofilms.
Incidence and Diagnostic Yield of Repeat Urine Culture in Hospitalized Patients: an Opportunity for Diagnostic Stewardship
Authors: Foong Kap Sum , Munigala Satish , Jackups Ronald , Yarbrough Melanie L. , Burnham Carey-Ann D. , Warren David K.
Published: August 2019

There is limited knowledge on the incidence, diagnostic yield, and cost associated with inappropriate repeat urine cultures. The factors that affect repeat urine culturing practices are not well understood. We conducted a retrospective study of adult inpatients who had ≥1 urine culture performed during their hospitalization between January 2015 and February 2018. We analyzed the proportion of inappropriate repeat urine cultures performed <48 h after the index culture.
Influenza A Virus Protein NS1 Exhibits Strain-Independent Conformational Plasticity
Authors: Mitra Sayantan , Kumar Dilip , Hu Liya , Sankaran Banumathi , Moosa Mahdi Muhammad , Rice Andrew P. , Ferreon Josephine C. , Ferreon Allan Chris M. , Prasad B. V. Venkataram
Published: August 2019

IAV is responsible for several pandemics over the last century and continues to infect millions annually. The frequent rise in drug-resistant strains necessitates exploring novel targets for developing antiviral drugs that can reduce the global burden of influenza infection. Because of its critical role in the replication and pathogenesis of IAV, nonstructural protein 1 (NS1) is a potential target for developing antivirals. Previous studies suggested that NS1 adopts strain-dependent “open,” “semiopen,” and “closed” conformations. Here we show, based on three crystal structures, that NS1 irrespective of strain differences can adopt an open conformation. We further show that NS1 from different strains primarily exists in an open conformation in solution and binds to cellular proteins with a similar affinity. Together, our findings suggest that conformational polymorphism facilitated by a flexible linker is intrinsic to NS1, and this may be the underlying factor allowing NS1 to bind several cellular factors during IAV replication.
Measles Virus Forms Inclusion Bodies with Properties of Liquid Organelles
Authors: Zhou Yuqin , Su Justin M. , Samuel Charles E. , Ma Dzwokai
Published: August 2019

Measles virus remains a pathogen of significant global concern. Despite an effective vaccine, outbreaks continue to occur, and globally ∼100,000 measles-related deaths are seen annually. Understanding the molecular basis of virus-host interactions that impact the efficiency of virus replication is essential for the further development of prophylactic and therapeutic strategies. Measles virus replication occurs in the cytoplasm in association with discrete bodies, though little is known of the nature of the inclusion body structures. We recently established that the cellular protein WD repeat-containing protein 5 (WDR5) enhances MeV growth and is enriched in cytoplasmic viral inclusion bodies that include viral proteins responsible for RNA replication. Here, we show that MeV N and P proteins are sufficient to trigger the formation of WDR5-containing inclusion bodies, that these structures display properties characteristic of phase-separated liquid organelles, and that P phosphorylation together with the host dynein motor affect the efficiency of the liquid-liquid phase separation process.
Analysis of HIV-1 Matrix-Envelope Cytoplasmic Tail Interactions
Authors: Alfadhli Ayna , Staubus August O. , Tedbury Philip R. , Novikova Mariia , Freed Eric O. , Barklis Eric
Published: August 2019

The mechanism by which HIV-1 envelope (Env) protein trimers assemble into virus particles is poorly understood but involves an interaction between Env cytoplasmic tails (CTs) and the matrix (MA) domain of the structural precursor Gag (PrGag) proteins. We show here that direct binding of MA to Env CTs correlates with MA trimerization, suggesting models where MA lattices regulate CT interactions and/or MA-CT trimer-trimer associations increase the avidity of MA-CT binding. We also show that MA binding to RNA ligands impairs MA-CT binding, potentially by interfering with MA trimerization and/or directly or allosterically blocking MA-CT binding sites. Rough mapping implicated CT C-terminal helices in MA binding, in agreement with cell culture studies on MA-CT interactions. Our results indicate that targeting HIV-1 MA-CT interactions may be a promising avenue for antiviral therapy.
Finding of Agr Phase Variants in Staphylococcus aureus
Authors: Gor Vishal , Takemura Aya J. , Nishitani Masami , Higashide Masato , Medrano Romero Veronica , Ohniwa Ryosuke L. , Morikawa Kazuya
Published: August 2019

Staphylococcus aureus
is responsible for a broad range of infections. This pathogen has a vast arsenal of virulence factors at its disposal, but avirulent strains are frequently isolated as the cause of clinical infections. These isolates have a mutated
agr
locus and have been believed to have no evolutionary future. Here we show that a fraction of Agr-negative strains can repair their mutated
agr
locus with mechanisms resembling phase variation. The
agr
revertants sustain an Agr OFF state as long as they exist as a minority but can activate their Agr system upon phagocytosis. These revertant cells might function as a cryptic insurance strategy to survive immune-mediated host stress that arises during infection.
Structural Basis for the Differential Regulatory Roles of the PDZ Domain in C-Terminal Processing Proteases
Authors: Chueh Chuang-Kai , Som Nilanjan , Ke Lu-Chu , Ho Meng-Ru , Reddy Manjula , Chang Chung-I
Published: August 2019

Prc, also known previously as Tsp, is the founding member of the carboxyl-terminal processing protease (CTP) family of PDZ domain-containing proteases that include CtpA and CtpB. The substrate-binding PDZ domain is responsible for regulating the protease activity of CTP proteases; however, the regulatory role of PDZ domain is stimulatory in Prc but inhibitory in CtpA/B. By determining a series of crystal structures of Prc in the unliganded resting state, this study presents the structural basis for PDZ-dependent activation of Prc, the results of which explain the contrasting roles of the PDZ domain in the regulation of the protease activity of CTPs.
Disruption of Glycolysis by Nutritional Immunity Activates a Two-Component System That Coordinates a Metabolic and Antihost Response by Staphylococcus aureus
Authors: Párraga Solórzano Paola K. , Yao Jiangwei , Rock Charles O. , Kehl-Fie Thomas E.
Published: August 2019

Two-component regulatory systems enable bacteria to adapt to changes in their environment during infection by altering gene expression and coordinating antihost responses. Despite the critical role of two-component systems in bacterial survival and pathogenesis, the activating signals for most of these regulators remain unidentified. This is exemplified by ArlRS, a
Staphylococcus aureus
global regulator that contributes to virulence and to resisting host-mediated restriction of essential nutrients, such as manganese. In this report, we demonstrate that manganese starvation and the absence of glycolytic substrates activate ArlRS. Further investigations revealed that ArlRS is activated when the latter half of glycolysis is disrupted, suggesting that
S. aureus
monitors flux through the second half of this pathway. Host-imposed manganese starvation also induced the expression of pore-forming toxins in an ArlRS-dependent manner. Cumulatively, this work reveals that ArlRS acts as a sensor that links nutritional status, cellular metabolism, and virulence regulation.
The Cervicovaginal Microbiota-Host Interaction Modulates Chlamydia trachomatis Infection
Authors: Edwards Vonetta L. , Smith Steven B. , McComb Elias J. , Tamarelle Jeanne , Ma Bing , Humphrys Michael S. , Gajer Pawel , Gwilliam Kathleen , Schaefer Alison M. , Lai Samuel K. , Terplan Mishka , Mark Katrina S. , Brotman Rebecca M. , Forney Larry J. , Bavoil Patrik M. , Ravel Jacques
Published: August 2019

The vaginal microbiota is believed to protect women against
Chlamydia trachomatis
, the etiologic agent of the most prevalent sexually transmitted infection (STI) in developed countries. The mechanism underlying this protection has remained elusive. Here, we reveal the comprehensive strategy by which the cervicovaginal microbiota modulates host functions to protect against chlamydial infection, thereby providing a novel conceptual mechanistic understanding. Major implications of this work are that (i) the impact of the vaginal microbiota on the epithelium should be considered in future studies of chlamydial infection and other STIs and (ii) a fundamental understanding of the cervicovaginal microbiota’s role in protection against STIs may enable the development of novel microbiome-based therapeutic strategies to protect women from infection and improve vaginal and cervical health.
Identification of Primary Antimicrobial Resistance Drivers in Agricultural Nontyphoidal Salmonella enterica Serovars by Using Machine Learning
Authors: Maguire Finlay , Rehman Muhammad Attiq , Carrillo Catherine , Diarra Moussa S. , Beiko Robert G.
Published: August 2019

Antimicrobial resistance (AMR) represents an existential threat to the function of modern medicine. Genomics and machine learning methods are being increasingly used to analyze and predict AMR. This type of surveillance is very important to try to reduce the impact of AMR. Machine learning models are typically trained using genomic data, but the aspects of the genomes that they use to make predictions are rarely analyzed. In this work, we showed how, by using different types of machine learning models and performing this analysis, it is possible to identify the key genes underlying AMR in nontyphoidal
Salmonella
(NTS). NTS is among the leading cause of foodborne illness globally; however, AMR in NTS has not been heavily studied within the food chain itself. Therefore, in this work we performed a broad-scale analysis of the AMR in NTS isolates from commercial chicken farms and identified some priority AMR genes for surveillance.
Bacteroides fragilis Strain ZY-312 Defense against Cronobacter sakazakii-Induced Necrotizing Enterocolitis
In Vitro
and in a Neonatal Rat Model
Authors: Fan Hongying , Chen Zhenhui , Lin Ruqin , Liu Yangyang , Wu Xianbo , Puthiyakunnon Santhosh , Wang Ye , Zhu Bo , Zhang Qiwei , Bai Yang , Zhi Fachao
Published: August 2019

Cronobacter sakazakii
is an opportunistic pathogenic bacterium that can cause necrotizing enterocolitis (NEC). However, the mechanism of pathogenicity of
C. sakazakii
is largely unknown. Here we have now demonstrated that apoptotic and pyroptotic stimuli are effectors of
C. sakazakii
-induced NEC. Previously, we isolated a novel probiotic strain candidate from fecal samples from healthy infants and characterized it as
Bacteroides fragilis
strain ZY-312. Functional characterization reveals that ZY-312 inhibited
C. sakazakii
invasion, restoring epithelial barrier dysfunction, decreasing the expression of inflammatory cytokines, and reducing dual cell death (pyroptosis and apoptosis). Furthermore, the presence of ZY-132 was sufficient to hinder the adverse reaction seen with
C. sakazakii
in a
C. sakazakii
-induced NEC model. Taking the results together, our study demonstrated the utility of ZY-312 as a promising probiotic agent for the prevention of NEC.
Interesting pancreatic tumour in the background of Tuberous Sclerosis
Authors: Amarjothi JMV , Jesudason Jeyasudhahar , Ramasamy Villalan , Babu OL Naganath
Published: August 2019

Tuberous Sclerosis Complex (TSC) is easily discernible by a myriad of manifestations, most notably dermatological. It is associated with well known and recognised intra-abdominal tumours like angiomyolipoma of the kidney. However, rarer tumours like pancreatic neuroendocrine tumours can occur in the setting of TSC. A high index of suspicion is necessary to identify and treat these lesions early in their natural course. Early identification augurs well with complete surgical excision and excellent survival.
Retrograde ejaculation associated with quetiapine and treatment with low-dose imipramine
Authors: Roughley Matthew , Lyall Marc
Published: August 2019

Sexual side-effects are common among those using antipsychotic medication and may result in poor compliance and reduced quality of life. Retrograde ejaculation (RE) has been described occurring with a number of antipsychotic medications (thioridazine, risperidone, iloperidone and clozapine) but there are no guidelines regarding management of antipsychotic-associated RE. Imipramine has been suggested as a treatment for antipsychotic-associated RE in one small study of patients prescribed thioridazine and a case series of patients prescribed iloperidone. Quetiapine is a commonly used antipsychotic and is thought to be associated with less sexual side-effects relative to other antipsychotic medications. This case report describes a 25-year-old man with first episode psychosis who developed RE during treatment with quetiapine which improved with low-dose imipramine. This is the first description of RE occurring with quetiapine and successful treatment of quetiapine-associated RE with imipramine.