bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal folate depletion during early development and high fat feeding from weaning elicit similar changes in gene expression, but not in DNA methylation, in adult offspring
Authors: McKay Jill A. , Xie Long , Adriaens Michiel , Evelo Chris T. , Ford Dianne , Mathers John C.
Published: December 2016

Scope

The ‘Predictive Adaptive Response’ hypothesis suggests that the in utero environment when mismatched with the post‐natal environment can influence later life health. Underlying mechanisms are poorly understood, but may involve gene transcription changes regulated via epigenetic mechanisms.

Methods and results

In a 2 × 2 factorial design, female C57Bl/6 mice were randomised to low or normal folate diets (0.4 mg/2 mg folic acid/kg diet) prior to and during pregnancy and lactation with offspring randomised to high‐ or low‐fat diets at weaning. Genome‐wide gene expression and promoter DNA methylation were measured using microarrays in adult male livers. Maternal folate depletion and high fat intake post‐weaning influenced gene expression (1859 and 1532 genes, respectively) and promoter DNA methylation (201 and 324 loci, respectively) but changes in expression and methylation were poorly matched for both dietary interventions. Expression of 642 genes was altered in response to both maternal folate depletion and post‐weaning high fat feeding, treatments imposed separately. In addition, there was evidence that the combined dietary insult (i.e. maternal folate depletion followed by high fat post‐weaning) caused the largest expression change for most genes.

Conclusion

Our observations align with, and provide evidence in support of, a potential underlying mechanism for the ‘Predictive Adaptive Response’ hypothesis.
Evaluation of Altered Drug Pharmacokinetics in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation
Authors: Ha Michael A. , Sieg Adam C.
Published: December 2016

Extracorporeal membrane oxygenation (ECMO) is a life‐support modality used in patients with refractory cardiac and/or respiratory failure. A significant resurgence in the use ECMO has been seen in recent years as a result of substantial improvements in technology and survival benefit. With expanding ECMO use, a better understanding of how ECMO affects drug pharmacokinetics (PK) is necessary. The vast majority of PK studies in patients receiving ECMO have been conducted within neonatal or pediatric populations or within a controlled environment (e.g., in vitro or ex vivo). Because of significant differences in absorption, distribution, metabolism, and excretion, it may be inappropriate to extrapolate these PK data to adults. Thus, the aims of this review are to evaluate the changes in drug PK during ECMO and to summarize the available PK data for common drugs used in the adult critically ill patients during ECMO support. A search of the PubMed (1965–July 2016), EMBASE (1965–July 2016), and Cochrane Controlled Trial Register databases was performed. All relevant studies describing PK alterations during ECMO in ex vivo experiments and in adults were included. Evaluation of the data indicated that drug PK in adults receiving ECMO support may be significantly altered. Factors influencing these alterations are numerous and have intricate relationships with each other but can generally be classified as ECMO circuit factors, drug factors, and patient factors. Commonly used drugs in these patients include antimicrobials, sedatives, and analgesics. PK data for most of these drugs are generally lacking; however, recent research efforts in this patient population have provided some limited guidance in drug dosing. With an improved understanding of altered drug PK secondary to ECMO therapy, optimization of pharmacotherapy within this critically ill population continues to move forward.
Facile deposition of high quality ferroelectric poly(vinylidene fluoride) thin films by thermally modulated spin coating
Authors: Dawson Noel M. , Atencio Phillip M. , Malloy Kevin J.
Published: December 2016

Direct deposition of high quality ferroelectric PVDF thin films using a modulated temperature spin coating method is demonstrated. The method is qualitatively guided from Flory‐Huggins theory of polymeric solutions and is general in applicability. Ferroelectric PVDF films with similar high structural and dielectric quality are deposited in environments ranging from 20 to 80% relative humidity on polar and non‐polar surfaces. The films do not show the presence of the non‐ferroelectric α‐phase. Resultant films have rms roughness values lower than 16 nm and remnant polarizations up to 6.5 µC cm−2. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 221–227
Shortest and secure routing protocol for multi‐hop cellular networks (SSRP‐MCN)
Authors: Othmen Salwa , Rekik Malek , Zarai Faouzi , Belghith Aymen , Kamoun Lotfi
Published: December 2016

Nowadays, many advanced are developed and become available for users. So, the demand for a higher data rate wireless access significantly increases. For that reason, new cellular wireless networks have been introduced such as Worldwide Interoperability for Microwave Access (WiMAX), Long Term Evolution (LTE) and LTE‐advanced. However, the centralized topology of these technologies requires that the users have a direct connection to the Base Station (BS). Such topology suffers from congestion problem when a large number of users are communicating in the same time. To overcome the congestion problem, the Device‐to‐device and the mobile relays communications have been proposed to overcome the limitations of the conventional cellular architecture. These technologies can improve the cellular network capacity and reduce the infrastructure costs. However, security in multi‐hop cellular networks (MCNs) is a great challenge especially when other mobile nodes participate in the routing process. Existing works on this topic focus on ensuring security for routing information. However, most studies do not secure the data transmission after the route selection and do not simultaneously ensure all the security requirements. In this paper, we propose a new secure and reliable routing protocol for MCNs. The main objective of this protocol is to select only the trustworthy intermediate nodes to participate in the route construction. These trustworthy nodes perform the route discovery process in a secure way and so discover a secure path that does not contain any attacker as an intermediate node. The intermediate nodes of the selected route participate in establishing a group key. This key is used to secure the data transmission phase after route selection. To achieve anonymity, the BS assigns to each mobile that participates in the selected route a temporary identity. We evaluate our proposed protocol in terms of security using AVISPA tool, and we conduct some simulations using Network Simulator (NS‐2). The simulation results show that it is reliable and provides acceptable performance in terms of throughput, end‐to‐end delay and normalized routing load. Copyright © 2016 John Wiley & Sons, Ltd.
Modulation of meiotic homologous recombination by DNA helicases
Authors: Lorenz Alexander
Published: December 2016

DNA helicases are ATP‐driven motor proteins which translocate along DNA capable of dismantling DNA‐DNA interactions and/or removing proteins bound to DNA. These biochemical capabilities make DNA helicases main regulators of crucial DNA metabolic processes, including DNA replication, DNA repair, and genetic recombination. This budding topic will focus on reviewing the function of DNA helicases important for homologous recombination during meiosis, and discuss recent advances in how these modulators of meiotic recombination are themselves regulated. The emphasis is placed on work in the two model yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, which has vastly expanded our understanding of meiotic homologous recombination, a process whose correct execution is instrumental for healthy gamete formation, and thus functioning sexual reproduction. Copyright © 2016 John Wiley & Sons, Ltd.
Twelve weeks’ progressive resistance training combined with protein supplementation beyond habitual intakes increases upper leg lean tissue mass, muscle strength and extended gait speed in healthy older women
Authors: Francis Peter , Mc Cormack William , Toomey Clodagh , Norton Catherine , Saunders Jean , Kerin Emmet , Lyons Mark , Jakeman Philip
Published: December 2016

The age-related decline in functional capability is preceded by a reduction in muscle quality. The purpose of this study was to assess the combined effects of progressive resistance training (PRT) and protein supplementation beyond habitual intakes on upper leg lean tissue mass (LTM), muscle quality and functional capability in healthy 50–70 years women. In a single-blinded, randomized, controlled design, 57 healthy older women (age 61.1 ± 5.1 years, 1.61 ± 0.65 m, 65.3 ± 15.3 kg) consumed 0.33 g/kg body mass of a milk-based protein matrix (PRO) for 12 weeks. Of the 57 women, 29 also engaged in a PRT intervention (PRO + PRT). In comparison to the PRO group (n = 28), those in the PRO + PRT group had an increase in upper leg LTM [0.04 (95% CI −0.07 to 0.01) kg vs. 0.13 (95% CI 0.08–0.18) kg, P = 0.027], as measured by Dual-energy X-ray absorptiometry; an increase in knee extensor (KE) torque [−1.6 (95% CI −7.3 to 4.4 N m) vs. 10.2 (95% CI 4.3–15.8 N m), P = 0.007], as measured from a maximal voluntary isometric contraction (Con-Trex MJ; CMV AG); and an increase in extended gait speed [-0.01 (95% CI −0.52–0.04) m s−1 vs. 0.10 (95% CI 0.05–0.22) m s−1, P = 0.001] as measured from a maximal 900 m effort. There was no difference between groups in the time taken to complete 5 chair rises or the number of chair rises performed in 30 s (P > 0.05). PRT in healthy older women ingesting a dietary protein supplement is an effective strategy to improve upper leg LTM, KE torque and extended gait speed in healthy older women.
Análisis de series de tiempo en el pronóstico de la demanda de almacenamiento de productos perecederos
Authors: Contreras Juárez Arturo , Atziry Zuñiga Catya , Martínez Flores José Luis , Sánchez Partida Diana
Published: December 2016

Los pronósticos son una herramienta que proporciona un estimado cuantitativo de la probabilidad de eventos futuros. La relevancia de incorporar pronósticos en la demanda de almacenamiento en productos perecederos dentro de la cadena de frio deriva de su importancia económica y social. Este caso de estudio presenta una empresa con tendencia de crecimiento dedicada al almacenamiento de productos perecederos e incorpora técnicas de pronósticos de series de tiempo, en el volumen de ingreso y egreso de los productos en una cámara frigorífica, con el fin de estimar el volumen de almacenamiento para prever los requerimientos de instalaciones adicionales, personal y materiales necesarios para la movilidad de los productos.
Clinical Characteristics, Health Care Utilization and Costs Among Men with Primary or Secondary Hypogonadism in a US Commercially Insured Population
Authors: Grabner Michael , Bodhani Amit , Khandelwal Nikhil , Palli Swetha , Bonine Nicole , Khera Mohit
Published: December 2016

Introduction

Hypogonadism is broadly associated with increases in chronic comorbid conditions and health care costs. Little is known about the specific impact of primary and secondary hypogonadism on health care costs.

Aim

To characterize the health care cost and utilization burden of primary and secondary hypogonadism in a population of US men with commercial insurance.

Methods

Newly diagnosed patients with International Classification of Diseases, Ninth Revision, Clinical Modification codes associated with specific medical conditions known to have a high prevalence of testosterone deficiency (ie, relating to primary or secondary hypogonadism) or who had fills for testosterone replacement therapy from January 1, 2007 through April 30, 2013 were identified in administrative claims data from the HealthCore Integrated Research Database. A cohort of patients without hypogonadism was matched on demographics and comorbidities. The matched hypogonadism and non-hypogonadism cohorts (n = 5,777 in each cohort) were compared during a 12-month follow-up period.

Main Outcome Measures

Direct health care expenditures and utilization were assessed for all causes and for hypogonadism-related claims. Costs included out-of-pocket patient expenditures and those paid by the insurer.

Results

Hypogonadism and matched non-hypogonadism cohorts were similar in demographics (mean age = 50 years) and diagnosed comorbid conditions in the 12 months preceding the index date. In the year after the index date, mean all-cause expenditures for patients with hypogonadism increased by 62% (from $5,425 to $8,813) compared with 25% for the matched controls (from $4,786 to $5,992; P < .01 for follow-up difference between groups). Approximately 16% of total mean costs ($1,377), primarily outpatient and pharmacy costs, were identifiable as related to hypogonadism.

Conclusion

These data from a population of US men with commercial insurance coverage showed a greater resource use burden for patients with primary and secondary hypogonadism compared with similar patients without hypogonadism. Additional management might be required to address unmet need and decrease the cost burden for patients with hypogonadism.
Diversity and taxonomy ofChaetomiumand chaetomium-like fungi from indoor environments
Authors: Wang X.W. , Houbraken J. , Groenewald J.Z. , Meijer M. , Andersen B. , Nielsen K.F. , Crous P.W. , Samson R.A.
Published: December 2016

During a study of indoor fungi, 145 isolates belonging toChaetomiaceaewere cultured from air, swab and dust samples from 19 countries. Based on the phylogenetic analyses of DNA-directed RNA polymerase II second largest subunit (rpb2), β-tubulin (tub2), ITS and 28S large subunit (LSU) nrDNA sequences, together with morphological comparisons with related genera and species, 30 indoor taxa are recognised, of which 22 represent known species, seven are described as new, and one remains to be identified to species level. In our collection, 69 % of the indoor isolates with six species cluster with members of theChaetomium globosumspecies complex, representingChaetomium sensu stricto. The other indoor species fall into nine lineages that are separated from each other with several known chaetomiaceous genera occurring among them. No generic names are available for five of those lineages, and the following new genera are introduced here:Amesiawith three indoor species,Arcopiluswith one indoor species,Collariellawith four indoor species,Dichotomopiluswith seven indoor species andOvatosporawith two indoor species. The generic concept ofBotryotrichumis expanded to includeEmilmuelleriaand the chaetomium-like speciesB. muromum(=Ch. murorum) in which two indoor species are included. The generic concept ofSubramaniulais expanded to include several chaetomium-like taxa as well as one indoor species.Humicolais recognised as a distinct genus including two indoor taxa. According to this study,Ch. globosumis the most abundantChaetomiaceaeindoor species (74/145), followed byCh. cochliodes(17/145),Ch. elatum(6/145) andB. piluliferum(5/145). The morphological diversity of indoorChaetomiaceaeas well as the morphological characteristics of the new genera are described and illustrated. This taxonomic study redefines the generic concept ofChaetomiumand provides new insight into the phylogenetic relationships among different genera withinChaetomiaceae.
Unusual diagnosis in a patient with minor ankle trauma
Authors: Piggott Zoë , Clark Donna
Published: December 2016

We present the case of a 23 year-old male who sustained an anterior tibial artery pseudoaneurysm after an apparently innocuous soccer injury. The patient presented with sudden onset severe pain and swelling one week after the injury. The diagnosis was made using duplex ultrasound, and confirmed with CT angiography. Definitive management consisted of endovascular platinum microcoiling. One year later, the patient is asymptomatic and remains active. A review of the epidemiology, diagnosis, and treatment of arterial pseudoaneurysm is presented. Bedside ultrasound in the emergency department may be a useful adjunct in the early identification of pseudoaneurysms.
Dietary inflammatory index and prostate cancer risk in a case–control study in Mexico
Authors: Vázquez-Salas Ruth A. , Shivappa Nitin , Galván-Portillo Marcia , López-Carrillo Lizbeth , Hébert James R. , Torres-Sánchez Luisa
Published: December 2016

Recent evidence suggests that a pro-inflammatory diet could be associated with prostate cancer (PC) risk. To evaluate the association between dietary inflammatory index (DII) and PC risk as well as aggressiveness, we conducted a case–control study in Mexico City. Cases were 394 individuals with incident, histologically confirmed PC, who were matched by age (±5 years) with 794 population controls. Dietary information was obtained through a semi-quantitative FFQ with a 3-year frame of reference before diagnosis, for cases, or interview, for controls. On the basis of twenty-eight food parameters, we estimated the energy-adjusted DII (E-DII). According to the Gleason score at diagnosis, PC cases were categorised as high (≥8), moderate (=7) and low (≤6) PC risk. Independent, unconditional logistic regression models adjusted for potential confounders were used to estimate PC risk and PC aggressiveness. There were no significant associations between overall PC risk and E-DII (OR3rd v. 1st tertile 1·18; 95 % CI 0·85, 1·63; P=0·33) or among men with high-risk PC (Gleason≥8) (OR 1·46; 95 % CI 0·88, 2·42; P=0·14). These results do not support the hypothesis that a pro-inflammatory diet is related to PC risk and PC aggressiveness. However, further studies with larger sample sizes, with sufficient statistical power and of varying designs should be conducted to address this hypothesis.
Barrio Women and Energopower in Medellín, Colombia
Authors: FERNANDO JUAN , ATEHORTÚA VELÁSQUEZ
Published: December 2016

This article argues that the prepaid energy system put into operation in Medellín and across Colombia worked as an expression of ‘energopower’; that is, energy as a means to govern societies. The article uses press archives and company statements, official statistics and group interviews to show how energopower operates in Medellín along three lines: that Empresas Públicas de Medellín, the city's public utility company, encouraged disconnected and displaced people as new buyers of prepaid energy services instead of citizens entitled to those services; that the implementation of the prepaid energy system coincided with the vertiginous capitalisation that allowed the city to fund its ‘Social Urbanism’ and EPM to expand operations across Colombia and other countries in Latin America; and, that prepaid electricity as a tool of energopower subjugated displaced and disconnected populations to new forms of affordability that promptedbarriowomen to understand and oppose its disciplining methods of domination.
Characterization of cyclin-dependent kinases and Cdc2/Cdc28 kinase subunits inTrichomonas vaginalis
Authors: AMADOR ERICK , LÓPEZ-PACHECO KARLA , MORALES NATALY , CORIA ROBERTO , LÓPEZ-VILLASEÑOR IMELDA
Published: December 2016

Cyclin-dependent kinases (CDKs) have important roles in regulating key checkpoints between stages of the cell cycle. Their activity is tightly regulated through a variety of mechanisms, including through binding with cyclin proteins and the Cdc2/Cdc28 kinase subunit (CKS), and their phosphorylation at specific amino acids. Studies of the components involved in cell cycle control in parasitic protozoa are limited.Trichomonas vaginalisis the causative agent of trichomoniasis in humans and is therefore important in public health; however, some of the basic biological processes used by this organism have not been defined. Here, we characterized proteins potentially involved in cell cycle regulation inT. vaginalis. Three genes encoding protein kinases were identified in theT. vaginalisgenome, and the corresponding recombinant proteins (TvCRK1, TvCRK2, TvCRK5) were studied. These proteins displayed similar sequence features to CDKs. Two genes encoding CKSs were also identified, and the corresponding recombinant proteins were found to interact with TvCRK1 and TvCRK2 by a yeast two-hybrid system. One putative cyclin B protein fromT. vaginaliswas found to bind to and activate the kinase activities of TvCRK1 and TvCRK5, but not TvCRK2. This work is the first characterization of proteins involved in cell cycle control inT. vaginalis.
LA EROSIÓN DEL PODER DE LA ÉLITE EN CHILE ENTRE 1913 Y 1970. UNA APROXIMACIÓN DESDE LOS INGRESOS DEL 1%
Authors: Weber Javier Rodríguez
Published: December 2016

Over the last few years, the idea that some of the central problems of Latin American development are a consequence of the excessive power of the elites has regained influence. Nevertheless, this neoinstitutionalist approach has been criticized because of its excessive determinism and the fact that it doesn’t pay enough attention to the periods when elite’s power was eroded. The present paper analyzes one of these cases, which occurred in Chile between 1913 and 1973. The income share of the top 1% is used as a proxy for the elite’s power. New quantitative evidence on incomes for different groups –the 1% and wage earners– is integrated into an analytic narrative on the conflictive relation between the elite and other political and social actors.
Effect of transfection and co-incubation of bovine sperm with exogenous DNA on sperm quality and functional parameters for its use in sperm-mediated gene transfer
Authors: Arias María Elena , Sánchez-Villalba Esther , Delgado Andrea , Felmer Ricardo
Published: December 2016

Sperm-mediated gene transfer (SMGT) is based on the capacity of sperm to bind exogenous DNA and transfer it into the oocyte during fertilization. In bovines, the progress of this technology has been slow due to the poor reproducibility and efficiency of the production of transgenic embryos. The aim of the present study was to evaluate the effects of different sperm transfection systems on the quality and functional parameters of sperm. Additionally, the ability of sperm to bind and incorporate exogenous DNA was assessed. These analyses were carried out by flow cytometry and confocal fluorescence microscopy, and motility parameters were also evaluated by computer-assisted sperm analysis (CASA). Transfection was carried out using complexes of plasmid DNA with Lipofectamine, SuperFect and TurboFect for 0.5, 1, 2 or 4 h. The results showed that all of the transfection treatments promoted sperm binding and incorporation of exogenous DNA, similar to sperm incorporation of DNA alone, without affecting the viability. Nevertheless, the treatments and incubation times significantly affected the motility parameters, although no effect on the integrity of DNA or the levels of reactive oxygen species (ROS) was observed. Additionally, we observed that transfection using SuperFect and TurboFect negatively affected the acrosome integrity, and TurboFect affected the mitochondrial membrane potential of sperm. In conclusion, we demonstrated binding and incorporation of exogenous DNA by sperm after transfection and confirmed the capacity of sperm to spontaneously incorporate exogenous DNA. These findings will allow the establishment of the most appropriate method [intracytoplasmic sperm injection (ICSI) orin vitrofertilization (IVF)] of generating transgenic embryos via SMGT based on the fertilization capacity of transfected sperm.
Increased vascular occlusion in patients with pseudoxanthoma elasticum
Authors: Pingel Simon , Pausewang Kristin Solveig , Passon Sebastian Gorgonius , Blatzheim Anna Katharina , Gliem Martin , Issa Peter Charbel , Hendig Doris , Horlbeck Fritz , Tuleta Izabela , Nickenig Georg , Schahab Nadjib , Skowasch Dirk , Schaefer Christian Alexander
Published: December 2016

Abstract. Background: Pseudoxanthoma elasticum (PXE) is an autosomal recessive inherited multisystem disorder of the connective tissue caused by a loss-of-function mutation of the ABCC6 gene. It can affect the cardiovascular system, presumably leading to a high prevalence of atherosclerosis. Patients and methods: 46 PXE patients and 18 controls underwent an angiological examination consisting of measurement of ankle-brachial index (ABI), strain-gauge arterial reserve (SGAR), arterial resting perfusion, pulse wave index (PWI), central pulse wave velocity, and ultrasound examination. Results: With an average age of 51.4 ± 12.4 years, 35/46 (76.1 %) of the PXE patients had atherosclerotic lesions, and 10 of them (28.6 %) had a chronic vascular occlusion of one or more peripheral vessels. 34/46 (73.9 %) had a pathologic ABI < 0.9, 15/42 (35.7 %) had a pathological SGAR < 10 mL/100 mL tissue/min, and 23/38 (60.5 %) had a pathological PWI > 180. The differences between the groups were statistically significant for ABI, arterial reserve, and PWI. Conclusions: In PXE patients atherosclerosis was found with a much higher prevalence than expected. Moreover, they were at very high risk for total vessel occlusions.
Rise in Tornado Numbers per Outbreak May Not Be Tied to Warming
Authors: Wendel JoAnna
Published: December 2016

Scientists studying why previous research revealed a steadily increasing number of tornadoes in the United States per outbreak find an unexpected result.
Celebrating Pediatric Psychology and Pediatric Psychologists
Authors: Berry Sharon
Published: December 2016

This invited article is based on the 2016 Presidential Address presented by the author at the annual conference of the Society of Pediatric Psychology held in Atlanta, Georgia, on April 14–16, 2016. The purpose of the yearly presidential address is to welcome conference attendees, set the stage for the theme of the annual conference, and review a major focus of the president’s own scientific and clinical work in the field of pediatric psychology. This year, the author focused on celebrating the successes of the Society of Pediatric Psychology and its members. Special attention was paid to the various national leaders in the field and their work both within pediatric psychology and across the general field of health service psychology.
A Qualitative Analysis of the Impact of Childhood Cancer on the Lives of Siblings at School, in Extracurricular Activities, and With Friends
Authors: Samson Kate , Rourke Mary T. , Alderfer Melissa A.
Published: December 2016

The purpose of this study was to examine the ways in which siblings of children with cancer perceive childhood cancer to have influenced their lives at school, in extracurricular activities, and with friends—the various social contexts in which child development occurs external to the family system. The qualitative interviews of 33 purposively sampled siblings of children with cancer were analyzed using modified grounded theory. Siblings were 8–15 years old ( M = 11.6, SD = 1.9), and the child with cancer was on treatment or within 2 years of diagnosis. Most siblings reported that cancer led to changes at school (81%), in extracurricular activities (79%), and with friends (94%). Generally, siblings reported less time within each of these social domains and also changes in the content, character, or quality of their experiences. Positive changes (e.g., increased support at school, strengthened friendships) and negative changes (e.g., trouble concentrating, disrupted routines, insensitivity and awkwardness within interpersonal relationships) were both uncovered. Documenting the possibly subtle but important changes that cancer diagnosis and treatment cause within the lives of siblings of children with cancer provides valuable information upon which to inform clinical care efforts to meet the psychosocial needs of siblings. Psychosocial providers in pediatric oncology should join with parents, community providers, and schools in collaborative efforts to screen, monitor, and address the needs of siblings of children with cancer.
The Yersinia Type III secretion effector YopM Is an E3 ubiquitin ligase that induced necrotic cell death by targeting NLRP3
Authors: Wei Congwen , Wang Ying , Du Zongmin , Guan Kai , Cao Ye , Yang Huiying , Zhou Pengyu , Wu Feixiang , Chen Jiankang , Wang Penghao , Zheng Zirui , Zhang Pingping , Zhang Yanhong , Ma Shengli , Yang Ruifu , Zhong Hui , He Xiang
Published: December 2016

Yersinia pestis uses type III effector proteins to target eukaryotic signaling systems. The Yersinia outer protein (Yop) M effector from the Y. pestis strain is a critical virulence determinant; however, its role in Y. pestis pathogenesis is just beginning to emerge. Here we first identify YopM as the structural mimic of the bacterial IpaH E3 ligase family in vitro, and establish that the conserved CLD motif in its N-terminal is responsible for the E3 ligase function. Furthermore, we show that NLRP3 is a novel target of the YopM protein. Specially, YopM associates with NLRP3, and its CLD ligase motif mediates the activating K63-linked ubiquitylation of NLRP3; as a result, YopM modulates NLRP3-mediated cell necrosis. Mutation of YopM E3 ligase motif dramatically reduces the ability of Y. pestis to induce HMGB1 release and cell necrosis, which ultimately contributes to bacterial virulence. In conclusion, this study has identified a previously unrecognized role for YopM E3 ligase activity in the regulation of host cell necrosis and plague pathogenesis.
Digenic mutations of human OCRL paralogs in Dent’s disease type 2 associated with Chiari I malformation
Authors: Duran Daniel , Jin Sheng Chih , DeSpenza Tyrone , Nelson-Williams Carol , Cogal Andrea G , Abrash Elizabeth W , Harris Peter C , Lieske John C , Shimshak Serena JE , Mane Shrikant , Bilguvar Kaya , DiLuna Michael L , Günel Murat , Lifton Richard P , Kahle Kristopher T
Published: December 2016

OCRL1and its paralogINPP5Bencode phosphatidylinositol 5-phosphatases that localize to the primary cilium and have roles in ciliogenesis. Mutations inOCRL1cause the X-linked Dent disease type 2 (DD2; OMIM# 300555), characterized by low-molecular weight proteinuria, hypercalciuria, and the variable presence of cataracts, glaucoma and intellectual disability without structural brain anomalies. Disease-causing mutations inINPP5Bhave not been described in humans. Here, we report the case of an 11-year-old boy with short stature and an above-average IQ; severe proteinuria, hypercalciuria and osteopenia resulting in a vertebral compression fracture; and Chiari I malformation with cervico-thoracic syringohydromyelia requiring suboccipital decompression. Sequencing revealed a novel,de novoDD2-causing 462 bp deletion disrupting exon 3 ofOCRL1and a maternally inherited, extremely rare (ExAC allele frequency 8.4×10−6) damaging missense mutation inINPP5B(p.A51V). This mutation substitutes an evolutionarily conserved amino acid in the protein’s critical PH domain.In silicoanalyses of mutation impact predicted by SIFT, PolyPhen2, MetaSVM and CADD algorithms were all highly deleterious. Together, our findings report a novel association of DD2 with Chiari I malformation and syringohydromyelia, and document the effects of digenic mutation of humanOCRLparalogs. These findings lend genetic support to the hypothesis that impaired ciliogenesis may contribute to the development of Chiari I malformation, and implicates OCRL-dependent PIP3metabolism in this mechanism.
Multi-dimensional super-resolution imaging enables surface hydrophobicity mapping
Authors: Bongiovanni Marie N. , Godet Julien , Horrocks Mathew H. , Tosatto Laura , Carr Alexander R. , Wirthensohn David C. , Ranasinghe Rohan T. , Lee Ji-Eun , Ponjavic Aleks , Fritz Joelle V. , Dobson Christopher M. , Klenerman David , Lee Steven F.
Published: December 2016

Super-resolution microscopy allows biological systems to be studied at the nanoscale, but has been restricted to providing only positional information. Here, we show that it is possible to perform multi-dimensional super-resolution imaging to determine both the position and the environmental properties of single-molecule fluorescent emitters. The method presented here exploits the solvatochromic and fluorogenic properties of nile red to extract both the emission spectrum and the position of each dye molecule simultaneously enabling mapping of the hydrophobicity of biological structures. We validated this by studying synthetic lipid vesicles of known composition. We then applied both to super-resolve the hydrophobicity of amyloid aggregates implicated in neurodegenerative diseases, and the hydrophobic changes in mammalian cell membranes. Our technique is easily implemented by inserting a transmission diffraction grating into the optical path of a localization-based super-resolution microscope, enabling all the information to be extracted simultaneously from a single image plane.
Current crowding mediated large contact noise in graphene field-effect transistors
Authors: Karnatak Paritosh , Sai T. Phanindra , Goswami Srijit , Ghatak Subhamoy , Kaushal Sanjeev , Ghosh Arindam
Published: December 2016

The impact of the intrinsic time-dependent fluctuations in the electrical resistance at the graphene–metal interface or the contact noise, on the performance of graphene field-effect transistors, can be as adverse as the contact resistance itself, but remains largely unexplored. Here we have investigated the contact noise in graphene field-effect transistors of varying device geometry and contact configuration, with carrier mobility ranging from 5,000 to 80,000 cm2V−1s−1. Our phenomenological model for contact noise because of current crowding in purely two-dimensional conductors confirms that the contacts dominate the measured resistance noise in all graphene field-effect transistors in the two-probe or invasive four-probe configurations, and surprisingly, also in nearly noninvasive four-probe (Hall bar) configuration in the high-mobility devices. The microscopic origin of contact noise is directly linked to the fluctuating electrostatic environment of the metal–channel interface, which could be generic to two-dimensional material-based electronic devices.
The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by promoting proteasomal degradation of NLRP3
Authors: Song Hui , Liu Bingyu , Huai Wanwan , Yu Zhongxia , Wang Wenwen , Zhao Jing , Han Lihui , Jiang Guosheng , Zhang Lining , Gao Chengjiang , Zhao Wei
Published: December 2016

The NLRP3 inflammasome has a fundamental role in host defence against microbial pathogens and its deregulation may cause diverse inflammatory diseases. NLRP3 protein expression is a rate-limiting step for inflammasome activation, thus its expression must be tightly controlled to maintain immune homeostasis and avoid detrimental effects. However, how NLRP3 expression is regulated remains largely unknown. In this study, we identify E3 ubiquitin ligase TRIM31 as a feedback suppressor of NLRP3 inflammasome. TRIM31 directly binds to NLRP3, promotes K48-linked polyubiquitination and proteasomal degradation of NLRP3. Consequently, TRIM31 deficiency enhances NLRP3 inflammasome activation and aggravates alum-induced peritonitis in vivo. Furthermore, TRIM31 deficiency attenuates the severity of dextran sodium sulfate (DSS)-induced colitis, an inflammatory bowel diseases model in which NLRP3 possesses protective roles. Thus, our research describes a mechanism by which TRIM31 limits NLRP3 inflammasome activity under physiological conditions and suggests TRIM31 as a potential therapeutic target for the intervention of NLRP3 inflammasome related diseases.
Correction: Corrigendum: Identification of a 5-Methylcytosine Site that may Regulate C/EBPβ Binding and Determine Tissue-Specific Expression of the BPI Gene in Piglets
Authors: Sun Li , Wang Jing , Yin Xuemei , Sun Shouyong , Zi Chen , Zhu Guoqiang , Wu Shenglong , Bao Wenbin
Published: December 2016

Scientific Reports 6: Article number: 28506; published online: 24 June 2016; updated: 08 December 2016. In this Article the Authors incorrectly stated that they had developed a novel method termed bisulfite amplicon sequencing (BSAS). The method was reported by Masser et al. (reference 18 in the Article).
Optimal generation of spatially coherent soft X-ray isolated attosecond pulses in a gas-filled waveguide using two-color synthesized laser pulses
Authors: Jin Cheng , Hong Kyung-Han , Lin C. D.
Published: December 2016

We numerically demonstrate the generation of intense, low-divergence soft X-ray isolated attosecond pulses in a gas-filled hollow waveguide using synthesized few-cycle two-color laser waveforms. The waveform is a superposition of a fundamental and its second harmonic optimized such that highest harmonic yields are emitted from each atom. We then optimize the gas pressure and the length and radius of the waveguide such that bright coherent high-order harmonics with angular divergence smaller than 1 mrad are generated, for photon energy from the extreme ultraviolet to soft X-rays. By selecting a proper spectral range enhanced isolated attosecond pulses are generated. We study how dynamic phase matching caused by the interplay among waveguide mode, neutral atomic dispersion, and plasma effect is achieved at the optimal macroscopic conditions, by performing time-frequency analysis and by analyzing the evolution of the driving laser’s electric field during the propagation. Our results, when combined with the on-going push of high-repetition-rate lasers (sub- to few MHz’s) may eventually lead to the generation of high-flux, low-divergence soft X-ray tabletop isolated attosecond pulses for applications.
Effect of TREM-1 blockade and single nucleotide variants in experimental renal injury and kidney transplantation
Authors: Tammaro A. , Kers J. , Emal D. , Stroo I. , Teske G. J. D. , Butter L. M. , Claessen N. , Damman J. , Derive M. , Navis G. , Florquin S. , Leemans J. C. , Dessing M. C.
Published: December 2016

Renal ischemia reperfusion (IR)-injury induces activation of innate immune response which sustains renal injury and contributes to the development of delayed graft function (DGF). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory evolutionary conserved pattern recognition receptor expressed on a variety of innate immune cells. TREM-1 expression increases following acute and chronic renal injury. However, the function of TREM-1 in renal IR is still unclear. Here, we investigated expression and function of TREM-1 in a murine model of renal IR using different TREM-1 inhibitors: LP17, LR12 and TREM-1 fusion protein. In a human study, we analyzed the association of non-synonymous single nucleotide variants in the TREM1 gene in a cohort comprising 1263 matching donors and recipients with post-transplant outcomes, including DGF. Our findings demonstrated that, following murine IR, renal TREM-1 expression increased due to the influx of Trem1 mRNA expressing cells detected by in situ hybridization. However, TREM-1 interventions by means of LP17, LR12 and TREM-1 fusion protein did not ameliorate IR-induced injury. In the human renal transplant cohort, donor and recipient TREM1 gene variant p.Thr25Ser was not associated with DGF, nor with biopsy-proven rejection or death-censored graft failure. We conclude that TREM-1 does not play a major role during experimental renal IR and after kidney transplantation.
Evolution of the NET (NocA, Nlz, Elbow, TLP-1) protein family in metazoans: insights from expression data and phylogenetic analysis
Authors: Pereira Filipe , Duarte-Pereira Sara , Silva Raquel M. , da Costa Luís Teixeira , Pereira-Castro Isabel
Published: December 2016

The NET (for NocA, Nlz, Elbow, TLP-1) protein family is a group of conserved zinc finger proteins linked to embryonic development and recently associated with breast cancer. The members of this family act as transcriptional repressors interacting with both class I histone deacetylases and Groucho/TLE co-repressors. In Drosophila, the NET family members Elbow and NocA are vital for the development of tracheae, eyes, wings and legs, whereas in vertebrates ZNF703 and ZNF503 are important for the development of the nervous system, eyes and limbs. Despite the relevance of this protein family in embryogenesis and cancer, many aspects of its origin and evolution remain unknown. Here, we show that NET family members are present and expressed in multiple metazoan lineages, from cnidarians to vertebrates. We identified several protein domains conserved in all metazoan species or in specific taxonomic groups. Our phylogenetic analysis suggests that the NET family emerged in the last common ancestor of cnidarians and bilaterians and that several rounds of independent events of gene duplication occurred throughout evolution. Overall, we provide novel data on the expression and evolutionary history of the NET family that can be relevant to understanding its biological role in both normal conditions and disease.
Totally embedded hybrid thin films of carbon nanotubes and silver nanowires as flat homogenous flexible transparent conductors
Authors: Pillai Suresh Kumar Raman , Wang Jing , Wang Yilei , Sk Md Moniruzzaman , Prakoso Ari Bimo , Rusli  , Chan-Park Mary B.
Published: December 2016

There is a great need for viable alternatives to today’s transparent conductive film using largely indium tin oxide. We report the fabrication of a new type of flexible transparent conductive film using silver nanowires (AgNW) and single-walled carbon nanotube (SWCNT) networks which are fully embedded in a UV curable resin substrate. The hybrid SWCNTs-AgNWs film is relatively flat so that the RMS roughness of the top surface of the film is 3 nm. Addition of SWCNTs networks make the film resistance uniform; without SWCNTs, sheet resistance of the surface composed of just AgNWs in resin varies from 20 Ω/sq to 107 Ω/sq. With addition of SWCNTs embedded in the resin, sheet resistance of the hybrid film is 29 ± 5 Ω/sq and uniform across the 47 mm diameter film discs; further, the optimized film has 85% transparency. Our lamination-transfer UV process doesn’t need solvent for sacrificial substrate removal and leads to good mechanical interlocking of the nano-material networks. Additionally, electrochemical study of the film for supercapacitors application showed an impressive 10 times higher current in cyclic voltammograms compared to the control without SWCNTs. Our fabrication method is simple, cost effective and enables the large-scale fabrication of flat and flexible transparent conductive films.
Subchronic perfluorooctanesulfonate (PFOS) exposure induces elevated mutant frequency in an in vivo λ transgenic medaka mutation assay
Authors: Chen Yuanhong , Hu Wei , Huang Changjiang , Hua Shushan , Wei Qihao , Bai Chenglian , Chen Jiangfei , Norris Michelle B. , Winn Richard , Yang Dongren , Dong Qiaoxiang
Published: December 2016

Perfluorooctanesulfonate (PFOS) has been widely detected in the environment, wildlife and humans, but few studies have ever examined its mutagenic effect in vivo. In the present study, we use a transgenic fish model, the λ transgenic medaka, to evaluate the potential mutagenicity of PFOS in vivo following a subchronic exposure of 30 days. The mutant frequency of cII target gene was 3.46 × 10−5 in liver tissue from control fish, which increased by 1.4-fold to 4.86 × 10−5 in fish exposed to 6.7 μg/L PFOS, 1.55-fold to 5.36 × 10−5 in fish exposed to 27.6 μg/L PFOS, and 2.02-fold to 6.99 × 10−5 in fish exposed to 87.6 μg/L PFOS. This dose-dependent increase of mutant frequency was also accompanied with mutational spectrum changes associated with PFOS exposure. In particular, PFOS-induced mutation was characterized by +1 frameshift mutations, which increased from 0% in control fish to 13.2% in fish exposed to 27.6 μg/L PFOS and 14.6% in fish exposed to 87.6 μg/L PFOS. Our findings provide the first evidence of PFOS’s mutagenicity in an aquatic model system. Given the fact that most conventional mutagenic assays were negative for PFOS, we propose that PFOS-induced mutation in liver tissue of λ transgenic medaka may be mediated through compromised liver function.
Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles: delivery and bioactivity in pancreatic cancer cells
Authors: Cogoi S. , Jakobsen U. , Pedersen E. B. , Vogel S. , Xodo L. E.
Published: December 2016

KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription factor essential for KRAS transcription. It is based on the use of palmitoyl-oleyl-phosphatidylcholine (POPC) liposomes functionalized with lipid-modified G4-decoy oligonucleotides and a lipid-modified cell penetrating TAT peptide. The potency of the strategy in pancreatic cancer cells is demonstrated by cell cytometry, confocal microscopy, clonogenic and qRT-PCR assays.
Designing Multipolar Resonances in Dielectric Metamaterials
Authors: Butakov Nikita A. , Schuller Jon A.
Published: December 2016

Dielectric resonators form the building blocks of nano-scale optical antennas and metamaterials. Due to their multipolar resonant response and low intrinsic losses they offer design flexibility and high-efficiency performance. These resonators are typically described in terms of a spherical harmonic decomposition with Mie theory. In experimental realizations however, a departure from spherical symmetry and the use of high-index substrates leads to new features appearing in the multipolar response. To clarify this behavior, we present a systematic experimental and numerical characterization of Silicon disk resonators. We demonstrate that for disk resonators on low-index quartz substrates, the electric and magnetic dipole modes are easily identifiable across a wide range of aspect-ratios, but that higher order peaks cannot be unambiguously associated with any specific multipolar mode. On high-index Silicon substrates, even the fundamental dipole modes do not have a clear association. When arranged into arrays, resonances are shifted and pronounced preferential forward and backward scattering conditions appear, which are not as apparent in individual resonators and may be associated with interference between multipolar modes. These findings present new opportunities for engineering the multipolar scattering response of dielectric optical antennas and metamaterials, and provide a strategy for designing nano-optical components with unique functionalities.
Human adipose mesenchymal stem cell-derived exosomal-miRNAs are critical factors for inducing anti-proliferation signalling to A2780 and SKOV-3 ovarian cancer cells
Authors: Reza Abu Musa Md Talimur , Choi Yun-Jung , Yasuda Hideyo , Kim Jin-Hoi
Published: December 2016

An enigmatic question exists concerning the pro- or anti-cancer status of mesenchymal stem cells (MSCs). Despite growing interest, this question remains unanswered, and the debate became intensified with new evidences backing each side. Here, we showed that human adipose MSC (hAMSC)-derived conditioned medium (CM) exhibited inhibitory effects on A2780 human ovarian cancer cells by blocking the cell cycle, and activating mitochondria-mediated apoptosis signalling. Explicitly, we demonstrated that exosomes, an important biological component of hAMSC-CM, could restrain proliferation, wound-repair and colony formation ability of A2780 and SKOV-3 cancer cells. Furthermore, hAMSC-CM-derived exosomes induced apoptosis signalling by upregulating different pro-apoptotic signalling molecules, such as BAX, CASP9, and CASP3, as well as downregulating the anti-apoptotic protein BCL2. More specifically, cancer cells exhibited reduced viability following fresh or protease-digested exosome treatment; however, treatment with RNase-digested exosomes could not inhibit the proliferation of cancer cells. Additionally, sequencing of exosomal RNAs revealed a rich population of microRNAs (miRNAs), which exhibit anti-cancer activities by targeting different molecules associated with cancer survival. Our findings indicated that exosomal miRNAs are important players involved in the inhibitory influence of hAMSC-CM towards ovarian cancer cells. Therefore, we believe that these comprehensive results will provide advances concerning ovarian cancer research and treatment.