bluuebunny/crossref_metadata_2025 huggingface dataset:
The MedITNet assessment framework: development and validation of a framework for improving risk management of medical IT networks
Authors: MacMahon Silvana Togneri , McCaffery Fergal , Keenan Frank
Published: April 2016

The use of networked medical devices can provide a number of benefits such as improved patient safety, a reduction in adverse events and reduced costs of care. Today, medical devices are increasingly designed for incorporation into a hospital's general IT network, which allows devices to exchange critical information. However, connecting devices in this way can introduce risks potentially negating the benefits to patients. While the IEC 80001‐1 standard has been developed to aid Healthcare Delivery Organisations (HDOs) in addressing these risks, HDOs often struggle to understand and implement the requirements. The MedITNet framework has been developed to allow HDOs to assess the capability of their risk management processes against the requirements of IEC 80001‐1. MedITNet provides a flexible assessment framework enabling HDOs to gain a greater understanding of the requirements of the standard and to improve risk management processes by determining their current state and highlighting areas for improvement. This paper examines the challenges faced by HDOs in the risk management of medical IT networks and briefly explains the components of the MedITNet framework and how the framework addresses these challenges. The use of Action Design Research (ADR) in the development and validation of MedITNet is also discussed focusing on a pilot implementation of the assessment method and expert review of the overall framework. The changes to the framework and its components as a result of the validation process are also discussed. Copyright © 2016 John Wiley & Sons, Ltd.
Rapid quantification of underivatized amino acids in plasma by hydrophilic interaction liquid chromatography (HILIC) coupled with tandem mass‐spectrometry
Authors: Prinsen Hubertus C. M. T. , Schiebergen‐Bronkhorst B. G. M. , Roeleveld M. W. , Jans J. J. M. , de Sain‐van der Velden M. G. M. , Visser G. , van Hasselt P. M. , Verhoeven‐Duif N. M.
Published: April 2016

Background

Amino acidopathies are a class of inborn errors of metabolism (IEM) that can be diagnosed by analysis of amino acids (AA) in plasma. Current strategies for AA analysis include cation exchange HPLC with post‐column ninhydrin derivatization, GC‐MS, and LC‐MS/MS‐related methods. Major drawbacks of the current methods are time‐consuming procedures, derivative problems, problems with retention, and MS‐sensitivity. The use of hydrophilic interaction liquid chromatography (HILIC) columns is an ideal separation mode for hydrophilic compounds like AA. Here we report a HILIC‐method for analysis of 36 underivatized AA in plasma to detect defects in AA metabolism that overcomes the major drawbacks of other methods.

Methods

A rapid, sensitive, and specific method was developed for the analysis of AA in plasma without derivatization using HILIC coupled with tandem mass‐spectrometry (Xevo TQ, Waters).

Results

Excellent separation of 36 AA (24 quantitative/12 qualitative) in plasma was achieved on an Acquity BEH Amide column (2.1×100 mm, 1.7 μm) in a single MS run of 18 min. Plasma of patients with a known IEM in AA metabolism was analyzed and all patients were correctly identified.

Conclusion

The reported method analyzes 36 AA in plasma within 18 min and provides baseline separation of isomeric AA such as leucine and isoleucine. No separation was obtained for isoleucine and allo‐isoleucine. The method is applicable to study defects in AA metabolism in plasma.
Design and Feasibility of an Intervention to Support Cancer Genetic Counselees in Informing their At‐Risk Relatives
Authors: de Geus Eveline , Eijzenga Willem , Menko Fred H. , Sijmons Rolf H. , de Haes Hanneke C. J. M. , Aalfs Cora M. , Smets Ellen M. A.
Published: April 2016

Cancer genetic counselees receive individualized information regarding heightened risks and medical recommendations which is also relevant for their at‐risk relatives. Unfortunately, counselees often insufficiently inform these relatives. We designed an intervention aimed at improving counselees’ knowledge regarding which at‐risk relatives to inform and what information to disclose, their motivation to disclose, and their self‐efficacy. The intervention, offered by telephone by trained psychosocial workers, is based on the principles of Motivational Interviewing. Phase 1 of the intervention covers agenda setting, exploration, and evaluation, and phase 2 includes information provision, enhancing motivation and self‐efficacy, and brainstorming for solutions to disseminate information within the family. Fidelity and acceptability of the intervention were assessed using recordings of intervention sessions and by counselee self‐report. A total of 144 counselees participated. Psychosocial workers (n = 5) delivered the intervention largely as intended. Counselees highly appreciated the content of the intervention and the psychosocial workers who delivered the intervention. In the sessions, psychosocial workers provided additional and/or corrective information, and brainstorming for solutions was performed in 70 %. These results indicate that this intervention is feasible and warrants testing in clinical practice. For this, a randomized controlled trial is currently in progress to test the intervention's efficacy.
The effect of postpartum intravenous immunoglobulins on the relapse rate among patients with multiple sclerosis
Authors: Brandt‐Wouters Evelyn , Gerlach Oliver H.H. , Hupperts Raymond M.M.
Published: April 2016

Objective

To evaluate the effect of intravenous immunoglobulins (IVIGs) on the expected increase in postpartum relapse rate (RR) among patients with multiple sclerosis (MS).

Methods

In a retrospective study, data were analyzed from patients with relapsing remitting MS who received postpartum IVIG at the Academic MS Center Limburg, Sittard‐Geleen, Netherlands, between April 2005 and January 2015. Patients received 10 g IVIG (Nanogam) for 3 consecutive days after childbirth, and then once monthly until 5 months after delivery. Data were compared with results from the Pregnancy in Multiple Sclerosis (PRIMS) I and II studies, which followed the natural outcomes of patients with MS with no intervention.

Results

Overall, 42 pregnancies were evaluated. The RR in the first 3 months after delivery was 0.48 ± 1.31, as compared with 1.2 in the PRIMS studies. The RR also remained low at 3–6, 6–9, and 9–12 months after delivery for patients who received IVIG.

Conclusion

Postpartum administration of IVIG could be beneficial in preventing childbirth‐associated relapses among patients with MS. It led to a substantial decrease in RR.
Predictors of stillbirths and neonatal deaths in rural western Uganda
Authors: Moyer Cheryl A. , Kolars Candace K. , Oppong Samuel A. , Bakari Ashura , Bell April , Busingye Priscilla
Published: April 2016

Objective

To explore pregnancy outcomes at a referral hospital in rural western Uganda.

Methods

A retrospective study was undertaken using data for all deliveries at Virika Hospital, Fort Portal, Uganda, between July 1, 2009, and October 22, 2011. A detailed review of delivery logs was conducted. Categories were created for obstetric risk factors (e.g. grand multipara, history of hypertension), maternal delivery complications (e.g. eclampsia, hemorrhage), and neonatal complications (e.g. fetal distress, birth defects).

Results

Overall, 4883 deliveries were included. Of the 517 neonates who did not survive, 430 (83.2%) had been stillborn. After controlling for parity, gestational age, obstetric risk factors, and neonatal complications, risk factors for stillbirth included maternal delivery complications (risk ratio [RR] 3.32, 95% confidence interval [CI] 2.34–4.71; P < 0.001) and living 51–100 km from the hospital (RR 3.37, 95% CI 2.41–4.74; P < 0.001). Risk factors for neonatal death included neonatal complications (RR 5.79, 95% CI 2.49–13.46; P = 0.001) and maternal delivery complications (RR 3.17, 95% CI 1.47–6.82; P = 0.003).

Conclusion

Qualified providers need to be deployed to rural areas of Uganda to facilitate the prompt identification and management of pregnancy, delivery, and neonatal complications.
Managing unethical behavior in organizations: The need for a behavioral business ethics approach
Authors: De Cremer David , Vandekerckhove Wim
Published: April 2016

Issues of morality and ethics have increasingly become more important in organizations and business settings. Traditionally, these issues of ethics and social responsibility in business settings have been discussed and commented on by prescriptive approaches that are grounded in philosophical traditions. Building on the idea that we need to develop a more comprehensive and complete understanding of the value that people assign to ethics and how it influences their actions and decisions, in the present article we discuss and review the importance and relevance of adopting also a descriptive approach that is grounded in the behavioral sciences (referred to as behavioral business ethics). This approach has the advantages to promote our insights into how people can show both good and bad behavior and why this is the case. Behavioral business ethics therefore represents an important research challenge for organizational researchers to pursue and engage more meaningfully with more prescriptive approaches.
Node-independent elementary signaling modes: A measure of redundancy in Boolean signaling transduction networks
Authors: SUN ZHONGYAO , ALBERT RÉKA
Published: April 2016

The redundancy of a system denotes the amount of duplicate components or mechanisms in it. For a network, especially one in which mass or information is being transferred from an origin to a destination, redundancy is related to the robustness of the system. Existing network measures of redundancy rely on local connectivity (e.g. clustering coefficients) or the existence of multiple paths. As in many systems there are functional dependencies between components and paths, a measure that not only characterizes the topology of a network, but also takes into account these functional dependencies, becomes most desirable.

We propose a network redundancy measure in a prototypical model that contains functionally dependent directed paths: a Boolean model of a signal transduction network. The functional dependencies are made explicit by using an expanded network and the concept of elementary signaling modes (ESMs). We define the redundancy of a Boolean signal transduction network as the maximum number of node-independent ESMs and develop a methodology for identifying all maximal node-independent ESM combinations. We apply our measure to a number of signal transduction network models and show that it successfully distills known properties of the systems and offers new functional insights. The concept can be easily extended to similar related forms, e.g. edge-independent ESMs.
Chaetozone corona (Polychaeta, Cirratulidae) in the Bay of Biscay: a new alien species for the North-east Atlantic waters?
Authors: Le Garrec Vincent , Grall Jacques , Chevalier Claire , Guyonnet Benjamin , Jourde Jérôme , Lavesque Nicolas , Bonifácio Paulo , Blake James A.
Published: April 2016

The cirratulid species Chaetozone corona is reported for the first time from the North-east Atlantic waters. Several specimens were collected during oceanographic surveys between 1996 and 2015 from soft bottom habitats along the coasts of Brittany (Western France). This species, originally described from the coast of California, was recently recorded for the first time from the Mediterranean Sea. We hypothesize that this species could have been recently introduced to the Atlantic coasts of Europe and colonized the northern coast of Bay of Biscay from the Loire estuary to the Iroise Sea. We discuss the potential vectors of introduction and the main environmental factors that could explain its current distribution. An identification key to all the known North-east Atlantic species of Chaetozone is given.
Deep-water taphonomy of vertebrate carcasses: a whale skeleton in the bathyal Santa Catalina Basin
Authors: Allison Peter A. , Smith Craig R. , Kukert Helmut , Deming Jody W. , Bennett Bruce A.
Published: April 2016

Taphonomic processes in deep-water environments differ markedly from those in shallow waters. These differences are illustrated by the preservational style of a large cetacean skeleton lying at the bottom of the Santa Catalina Basin in 1,240 m of water. The degree of skeletal articulation contrasts with that documented in the shallow North Sea where gas-filled, buoyant carcasses disarticulated during flotation. Increased hydrostatic pressure at greater depth is presumed to have prevented the whale carcass from floating and promoted increased levels of preservation. We present a model that relates gas evolution during decay to carcass buoyancy with depth. Application of this model may ultimately allow the degree of skeletal articulation to be used as a rough index of paleobathymetry.
The Use and Abuse of Theodicy
Authors: Tilley Terrence W.
Published: April 2016

The present essay distinguishes two ways to “settle” the problem of evil, “defense” and “theodicy,” as practiced in contemporary Christian philosophical theology. It argues that Christian theology can defend Christian belief from the charge of inconsistency, but that when it attempts to explain why and how God permits or wills evil in his world, it stumbles over denying the reality of evil or the goodness of God. The essay concludes by arguing that the Christian theologian cannot and should not attempt to make Christianity plausible by constructing theodicies but should concentrate on other methods of demonstrating the plausibility of Christianity.
Prevalence of neutralizing antibodies against West Nile virus (WNV) in monkeys (Ateles geoffroyi and Alouatta pigra) and crocodiles (Crocodylus acutus and C. acutus–C. moreletti hybrids) in Mexico
Authors: LOZA-RUBIO E. , ROJAS-ANAYA E. , LÓPEZ-RAMÍREZ R. DEL C. , SAIZ J. C. , ESCRIBANO-ROMERO E.
Published: April 2016

West Nile virus (WNV) is a mosquito-borne neurotropic viral pathogen maintained in an enzootic cycle between mosquitoes (vectors) and birds (natural hosts) with equids, humans, and other vertebrates acting as dead-end hosts. WNV activity in Mexico has been reported in several domestic and wild fauna and in humans, and the virus has been isolated from birds, mosquitoes, and humans. However, no serological studies have been conducted in monkeys, and only two in a limited number of crocodiles (Crocodylus moreletii). Here we present data on the prevalence of neutralizing antibodies against WNV in 53 healthy wild monkeys (49 Ateles geoffroyi and four Alouatta pigra), and 80 semi-captive healthy crocodiles (60 C. acutus and 20 C. acutus–C. moreletti hybrids) sampled during 2012. None of the monkey sera neutralized WNV, whereas 55% of the crocodile sera presented neutralizing antibodies against WNV. These results can contribute to the design of surveillance programmes in Mexico.
Simplified material assignment for cone beam computed tomography-based dose calculations of prostate radiotherapy with hip prostheses
Authors: Almatani Turki , Hugtenburg Richard P. , Lewis Ryan , Barley Susan , Edwards Mark
Published: April 2016

Objective

Cone beam computed tomography (CBCT) images contain more scatter than a conventional computed tomography (CT) image and therefore provide inaccurate Hounsfield units (HUs). Consequently, CBCT images cannot be used directly for dose calculation. The aim of this study is to enable dose calculations to be performed with the use of CBCT images taken during radiotherapy and potentially avoid the necessity of re-planning.

Methodology

A phantom and prostate cancer patient with a metallic prosthetic hip replacement were imaged using both CT and CBCT. The multilevel threshold algorithm was used to categorise pixel values in the CBCT images into segments of homogeneous HU. The variation in HU with position in the CBCT images was taken into consideration and the benefit of using a larger number of materials than typically used in previous work has been explored. This segmentation method relies upon the operator dividing the CBCT data into a set of volumes where the variation in the relationship between pixel values and HUs is small. A field-in-field treatment plan was generated from the CT of the phantom. An intensity-modulated radiation therapy plan was generated from CT images of the patient. These plans were then copied to the segmented CBCT datasets with identical settings and the doses were recalculated and compared.

Results

In the phantom study,γevaluation showed that the percentage of points falling in planning target volume, rectum and bladder withγ<1 (3%/3 mm) was 100%. In the patient study, increasing the number of bins to define the material type from seven materials to eight materials required 50% more operator time to improve the accuracy by 0·01% using pencil beam and collapsed cone and 0·05% when using Monte Carlo algorithms.

Conclusion

The segmentation of CBCT images using the method in this study can be used for dose calculation. For a simple phantom, 2 values of HU were needed to improve dose calculation accuracy. In challenging circumstances such as that of a prostate patient with hip prosthesis, 5 values of HU were found to be needed, giving a reasonable balance between dose accuracy and operator time.
Galectin-1 induces hepatocellular carcinoma EMT and sorafenib resistance by activating FAK/PI3K/AKT signaling
Authors: Zhang P-F , Li K-S , Shen Y-h , Gao P-T , Dong Z-R , Cai J-B , Zhang C , Huang X-Y , Tian M-X , Hu Z-Q , Gao D-M , Fan J , Ke A-W , Shi G-M
Published: April 2016

Galectin-1 (Gal-1) is involved in several pathological activities associated with tumor progression and chemoresistance, however, the role and molecular mechanism of Gal-1 activity in hepatocellular carcinoma (HCC) epithelial–mesenchymal transition (EMT) and sorafenib resistance remain enigmatic. In the present study, forced Gal-1 expression promoted HCC progression and sorafenib resistance. Gal-1 elevated αvβ3-integrin expression, leading to AKT activation. Moreover, Gal-1 overexpression induced HCC cell EMT via PI3K/AKT cascade activation. Clinically, our data revealed that Gal-1 overexpression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that Gal-1 may be a potential therapeutic target for HCC and a biomarker for predicting response to sorafenib treatment.
Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner
Authors: White Jason T. , Cross Eric W. , Burchill Matthew A. , Danhorn Thomas , McCarter Martin D. , Rosen Hugo R. , O’Connor Brian , Kedl Ross M.
Published: April 2016

Virtual memory cells (VM) are an antigen-specific, memory phenotype CD8 T-cell subset found in lymphoreplete, unchallenged mice. Previous studies indicated that VM cells were the result of homeostatic proliferation (HP) resembling the proliferation observed in a lymphopenic environment. Here we demonstrate that HP is ongoing in lymphoreplete mice, the degree of which is dictated by the number of naive CD8 T cells with a sufficiently high affinity for self-antigen interacting with peripheral IL-15. VM cell transcriptional profiles suggest a capacity to mediate protective immunity via antigen non-specific bystander killing, a function we show is dependent on IL-15. Finally, we show a VM-like population of human cells that accumulate with age and traffic to the liver, displaying phenotypic and functional attributes consistent with the bystander protective functions of VM cells identified in the mouse. These data identify developmental and functional attributes of VM cells, including their likely role in protective immunity.
Realistic noise-tolerant randomness amplification using finite number of devices
Authors: Brandão Fernando G. S. L. , Ramanathan Ravishankar , Grudka Andrzej , Horodecki Karol , Horodecki Michał , Horodecki Paweł , Szarek Tomasz , Wojewódka Hanna
Published: April 2016

Randomness is a fundamental concept, with implications from security of modern data systems, to fundamental laws of nature and even the philosophy of science. Randomness is called certified if it describes events that cannot be pre-determined by an external adversary. It is known that weak certified randomness can be amplified to nearly ideal randomness using quantum-mechanical systems. However, so far, it was unclear whether randomness amplification is a realistic task, as the existing proposals either do not tolerate noise or require an unbounded number of different devices. Here we provide an error-tolerant protocol using a finite number of devices for amplifying arbitrary weak randomness into nearly perfect random bits, which are secure against a no-signalling adversary. The correctness of the protocol is assessed by violating a Bell inequality, with the degree of violation determining the noise tolerance threshold. An experimental realization of the protocol is within reach of current technology.
CRL4Wdr70 regulates H2B monoubiquitination and facilitates Exo1-dependent resection
Authors: Zeng Ming , Ren Laifeng , Mizuno Ken'Ichi , Nestoras Konstantinos , Wang Haibin , Tang Zizhi , Guo Liandi , Kong Daochun , Hu Qiwen , He Qun , Du Lilin , Carr Antony M. , Liu Cong
Published: April 2016

Double-strand breaks repaired by homologous recombination (HR) are first resected to form single-stranded DNA, which binds replication protein A (RPA). RPA attracts mediators that load the Rad51 filament to promote strand invasion, the defining feature of HR. How the resection machinery navigates nucleosome-packaged DNA is poorly understood. Here we report that in Schizosaccharomyces pombe a conserved DDB1-CUL4-associated factor (DCAF), Wdr70, is recruited to DSBs as part of the Cullin4-DDB1 ubiquitin ligase (CRL4Wdr70) and stimulates distal H2B lysine 119 mono-ubiquitination (uH2B). Wdr70 deletion, or uH2B loss, results in increased loading of the checkpoint adaptor and resection inhibitor Crb253BP1, decreased Exo1 association and delayed resection. Wdr70 is dispensable for resection upon Crb253BP1 loss, or when the Set9 methyltransferase that creates docking sites for Crb2 is deleted. Finally, we establish that this histone regulatory cascade similarly controls DSB resection in human cells.
Epidermal Notch1 recruits RORγ+ group 3 innate lymphoid cells to orchestrate normal skin repair
Authors: Li Zhi , Hodgkinson Tom , Gothard Elizabeth J. , Boroumand Soulmaz , Lamb Rebecca , Cummins Ian , Narang Priyanka , Sawtell Amy , Coles Jenny , Leonov German , Reboldi Andrea , Buckley Christopher D. , Cupedo Tom , Siebel Christian , Bayat Ardeshir , Coles Mark C. , Ambler Carrie A.
Published: April 2016

Notch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epidermal Notch induces recruitment of immune cell subsets including RORγ+ ILC3s into wounded dermis; RORγ+ ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for RORγ+ ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNFα and the ILC3 recruitment chemokines CCL20 and CXCL13. TNFα, as a Notch1 effector, directs ILC3 localization and rates of wound healing. Altogether these findings suggest that Notch is a key stress/injury signal in skin epithelium driving innate immune cell recruitment and normal skin tissue repair.
Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes
Authors: Suh Alexander , Witt Christopher C. , Menger Juliana , Sadanandan Keren R. , Podsiadlowski Lars , Gerth Michael , Weigert Anne , McGuire Jimmy A. , Mudge Joann , Edwards Scott V. , Rheindt Frank E.
Published: April 2016

Parasite host switches may trigger disease emergence, but prehistoric host ranges are often unknowable. Lymphatic filariasis and loiasis are major human diseases caused by the insect-borne filarial nematodesBrugia,WuchereriaandLoa. Here we show that the genomes of these nematodes and seven tropical bird lineages exclusively share a novel retrotransposon, AviRTE, resulting from horizontal transfer (HT). AviRTE subfamilies exhibit 83–99% nucleotide identity between genomes, and their phylogenetic distribution, paleobiogeography and invasion times suggest that HTs involved filarial nematodes. The HTs between bird and nematode genomes took place in two pantropical waves, >25–22 million years ago (Myr ago) involving theBrugia/Wuchererialineage and >20–17 Myr ago involving theLoalineage. Contrary to the expectation from the mammal-dominated host range of filarial nematodes, we hypothesize that these major human pathogens may have independently evolved from bird endoparasites that formerly infected the global breadth of avian biodiversity.
Nonadditivity of critical Casimir forces
Authors: Paladugu Sathyanarayana , Callegari Agnese , Tuna Yazgan , Barth Lukas , Dietrich Siegfried , Gambassi Andrea , Volpe Giovanni
Published: April 2016

In soft condensed matter physics, effective interactions often emerge due to the spatial confinement of fluctuating fields. For instance, microscopic particles dissolved in a binary liquid mixture are subject to critical Casimir forces whenever their surfaces confine the thermal fluctuations of the order parameter of the solvent close to its critical demixing point. These forces are theoretically predicted to be nonadditive on the scale set by the bulk correlation length of the fluctuations. Here we provide direct experimental evidence of this fact by reporting the measurement of the associated many-body forces. We consider three colloidal particles in optical traps and observe that the critical Casimir force exerted on one of them by the other two differs from the sum of the forces they exert separately. This three-body effect depends sensitively on the distance from the critical point and on the chemical functionalisation of the colloid surfaces.
Differences in vulnerability of neurons and astrocytes to heme oxygenase-1 modulation: Implications for mitochondrial ferritin
Authors: Yu Xiaojun , Song Ning , Guo Xinli , Jiang Hong , Zhang Haoyun , Xie Junxia
Published: April 2016

Induction of the antioxidant enzyme heme oxygenase-1 (HO-1) was observed in both astrocytes and neurons in the substantia nigra of patients with Parkinson’s disease (PD). In the current study, we investigated whether HO-1 behaves differently between neurons and astrocytes under the condition of neurotoxicity related to PD. The results showed a time-dependent HO-1 upregulation in primary cultured ventral mesencephalon neurons and astrocytes treated with the mitochondria complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) or recombinant α-synuclein. However, HO-1 upregulation appeared much later in neurons than in astrocytes. The HO-1 inhibitor zinc protoporphyrin (ZnPP) aggravated MPP+- or α-synuclein-induced oxidative damage in both astrocytes and neurons, indicating that this HO-1 response was cytoprotective. For neurons, the HO-1 activator cobalt protoporphyrin IX (CoPPIX) exerted protective effects against MPP+ or α-synuclein during moderate HO-1 upregulation, but it aggravated damage at the peak of the HO-1 response. For astrocytes, CoPPIXalways showed protective effects. Higher basal and CoPPIX-induced mitochondrial ferritin (MtFt) levels were detected in astrocytes. Lentivirus-mediated MtFt overexpression rescued the neuronal damage induced by CoPPIX, indicating that large MtFt buffering capacity contributes to pronounced HO-1 tolerance in astrocytes. Such findings suggest that astrocyte-targeted HO-1 interventions and MtFt modulations have potential as novel pharmacological strategies in PD.
Fine-scale behavioural differences distinguish resource use by ecomorphs in a closed ecosystem
Authors: Hawley Kate L. , Rosten Carolyn M. , Christensen Guttorm , Lucas Martyn C.
Published: April 2016

Temporal differences in habitat use and foraging specialisms between ecomorphs represent aspects of behavioural phenotype that are poorly understood with regard to the origin and maintenance of ecological diversity. We tested the role of behaviour in resource use divergence of two Arctic charr (Salvelinus alpinus) phenotypes, a slim, putatively pelagic-dwelling morph and a robust, putatively littoral-dwelling generalist morph, over an annual cycle, using biotelemetry and stable isotopes. Pelagic morph charr exhibited significantly greater δC13 depletion, concordant with increased zooplanktivory, than for the Littoral morph. Although three-dimensional space-use of the morphs strongly overlapped, on average, the Littoral morph used that habitat 19.3% more than the Pelagic morph. Pelagic morph fish were significantly more active, further from the lake bed and at greater depth than Littoral fish (annual means respectively, Pelagic, 0.069BLs−1, 8.21 m and 14.11 m; Littoral, 0.047BLs−1, 5.87 m and 10.47 m). Patterns of habitat use differed between ecomorphs at key times, such as during autumn and at ice break, likely related to spawning and resumption of intensive foraging respectively. Extensive space-use overlap, but fine-scale differences in habitat use between charr ecomorphs, suggests the importance of competition for generating and maintaining polymorphism, and its potential for promoting reproductive isolation and evolution in sympatry.
Circulating microRNA profiles of Ebola virus infection
Authors: Duy Janice , Koehler Jeffrey W. , Honko Anna N. , Schoepp Randal J. , Wauquier Nadia , Gonzalez Jean-Paul , Pitt M. Louise , Mucker Eric M. , Johnson Joshua C. , O’Hearn Aileen , Bangura James , Coomber Moinya , Minogue Timothy D.
Published: April 2016

Early detection of Ebola virus (EBOV) infection is essential to halting transmission and adjudicating appropriate treatment. However, current methods rely on viral identification, and this approach can misdiagnose presymptomatic and asymptomatic individuals. In contrast, disease-driven alterations in the host transcriptome can be exploited for pathogen-specific diagnostic biomarkers. Here, we present for the first time EBOV-induced changes in circulating miRNA populations of nonhuman primates (NHPs) and humans. We retrospectively profiled longitudinally-collected plasma samples from rhesus macaques challenged via intramuscular and aerosol routes and found 36 miRNAs differentially present in both groups. Comparison of miRNA abundances to viral loads uncovered 15 highly correlated miRNAs common to EBOV-infected NHPs and humans. As proof of principle, we developed an eight-miRNA classifier that correctly categorized infection status in 64/74 (86%) human and NHP samples. The classifier identified acute infections in 27/29 (93.1%) samples and in 6/12 (50%) presymptomatic NHPs. These findings showed applicability of NHP-derived miRNAs to a human cohort, and with additional research the resulting classifiers could impact the current capability to diagnose presymptomatic and asymptomatic EBOV infections.
The germline-enriched Ppp1r36 promotes autophagy
Authors: Zhang Qinghua , Gao Maomao , Zhang Ying , Song Ying , Cheng Hanhua , Zhou Rongjia
Published: April 2016

Spermatogenesis is a highly regulated process during which haploid sperm cells are generated. Although autophagy is involved in the spermatogenesis process, the molecular pathways and regulations of autophagy in germ cell development remain elusive. Here, we showed that Ppp1r36, a regulatory subunit of protein phosphatase 1, is expressed during gonadal development, mainly in testes during spermatogenesis. Autophagy protein LC3 (microtubule associated protein 1 light chain 3), especially its active form LC3-II, had a similar expression pattern to Ppp1r36. Moreover, LC3-II level and puncta analysis showed that autophagy is up-regulated around 21 dpp (day postpartum) in postnatal testis, indicating a potential role of autophagy during the first wave of spermatogenesis. We demonstrated that Ppp1r36 promotes autophagosome formation upon starvation induction. Further autophagy flux analysis using a tandem fluorescent indicator, mCherry-GFP-LC3, confirmed that Ppp1r36 participated in autophagy. We further determined that Ppp1r36 is associated with Atg16L1 (autophagy related 16-like 1) in autophagy of starvation induction. Thus, our results uncover a potential role of the regulatory subunit Ppp1r36 of protein phosphatase 1 in enhancing autophagy during spermatogenesis.
CD14 in the TLRs signaling pathway is associated with the resistance to E. coli F18 in Chinese domestic weaned piglets
Authors: Wu Zhengchang , Liu Ying , Dong Wenhua , Zhu Guo-qiang , Wu Shenglong , Bao Wenbin
Published: April 2016

Escherichia coli F18 (E. coli F18) is mainly responsible for post-weaning diarrhea (PWD) in piglets. The genetic basis and regulatory mechanism of E. coli F18 resistance in Chinese domestic weaned piglets remain unclear. Meishan piglets were used as model animals to test their susceptibility to E. coli F18. By performing a comparative transcriptome study on duodenum tissues of sensitive and resistant pigs, we identified 198 differentially expressed genes (DEGs; 125 upregulated and 73 downregulated) in the resistant pigs. DEGs were predominately involved in immune system pathways, including the Toll-like receptor (TLR) signaling pathway. qPCR and western blot showed CD14, IFN-α, TLR4 and IL-1β, etc. in the TLR signaling pathway had significantly higher expression levels in lipopolysaccharide (LPS)-induced small intestinal epithelial cell lines (IPEC-J2) than those in normal IPEC-J2 cells. Immunohistochemical analysis showed the increased expression of CD14 gene in the E. coli F18-resistant individuals. After CD14 knockdown, the levels of cytokines IL-6 and IL-12 were significantly reduced in IPEC-J2 cell supernatants. The adhesion ability of F18ab strain with IPEC-J2 cells was significantly increased (p < 0.01). This study revealed the TLR signaling pathway, and especially CD14, probably plays an important role in resistance to E. coli F18 infection in Chinese domestic piglets.
Revealing the acute asthma ignorome: characterization and validation of uninvestigated gene networks
Authors: Riba Michela , Garcia Manteiga Jose Manuel , Bošnjak Berislav , Cittaro Davide , Mikolka Pavol , Le Connie , Epstein Michelle M. , Stupka Elia
Published: April 2016

Systems biology provides opportunities to fully understand the genes and pathways in disease pathogenesis. We used literature knowledge and unbiased multiple data meta-analysis paradigms to analyze microarray datasets across different mouse strains and acute allergic asthma models. Our combined gene-driven and pathway-driven strategies generated a stringent signature list totaling 933 genes with 41% (440) asthma-annotated genes and 59% (493) ignorome genes, not previously associated with asthma. Within the list, we identified inflammation, circadian rhythm, lung-specific insult response, stem cell proliferation domains, hubs, peripheral genes, and super-connectors that link the biological domains (Il6, Il1ß, Cd4, Cd44, Stat1, Traf6, Rela, Cadm1, Nr3c1, Prkcd, Vwf, Erbb2). In conclusion, this novel bioinformatics approach will be a powerful strategy for clinical and across species data analysis that allows for the validation of experimental models and might lead to the discovery of novel mechanistic insights in asthma.
Field trial of medicinal plant, Bidens pilosa, against eimeriosis in broilers
Authors: Chang Cicero Lee-Tian , Yang Cheng-Ying , Muthamilselvan Thangarasu , Yang Wen-Chin
Published: April 2016

Eimeriosis is a severe protozoan disease in poultry. Because of increasing concern about drug residue and drug resistance with the use of anticoccidial drugs, natural products are emerging as an alternative and complementary approach to control avian eimeriosis. Our previous publication showed that feed supplemented with B. pilosa (BP) was effective at combating chicken eimeriosis in experimental settings. However, its efficacy against chicken eimeriosis under field conditions is not known. Here, we investigated the efficacy of BP against eimeriosis on an organic chicken farm. We found that feed supplemented with BP, at the dose of 0.025% of feed or more, significantly reduced Eimeria infection. This treatment increased body weight gain and reduced feed conversion ratio, leading to superior growth performance. It lowered morbidity/mortality rate, decreased oocysts per gram of feces and gut pathology and augmented the anticoccidial index. Collectively, these data demonstrated the potential of BP to control chicken eimeriosis on chicken farms. BP can, therefore, be used as an effective means to control eimeriosis.
Posttranslational hypusination of the eukaryotic translation initiation factor-5A regulates Fusarium graminearum virulence
Authors: Martinez-Rocha Ana Lilia , Woriedh Mayada , Chemnitz Jan , Willingmann Peter , Kröger Cathrin , Hadeler Birgit , Hauber Joachim , Schäfer Wilhelm
Published: April 2016

Activation of eukaryotic translation initiation factor eIF5A requires a posttranslational modification, forming the unique amino acid hypusine. This activation is mediated by two enzymes, deoxyhypusine synthase, DHS, and deoxyhypusine hydroxylase, DOHH. The impact of this enzymatic complex on the life cycle of a fungal pathogen is unknown. Plant pathogenic ascomycetes possess a single copy of the eIF5A activated by hypusination. We evaluated the importance of imbalances in eIF5A hypusination in Fusarium graminearum, a devastating fungal pathogen of cereals. Overexpression of DHS leads to increased virulence in wheat, elevated production of the mycotoxin deoxynivalenol, more infection structures, faster wheat tissue invasion in plants and increases vegetatively produced conidia. In contrast, overexpression of DOHH completely prevents infection structure formation, pathogenicity in wheat and maize, leads to overproduction of ROS, reduced DON production and increased sexual reproduction. Simultaneous overexpression of both genes restores wild type-like phenotypes. Analysis of eIF5A posttranslational modification displayed strongly increased hypusinated eIF5A in DOHH overexpression mutant in comparison to wild type, and the DHS overexpression mutants. These are the first results pointing to different functions of differently modified eIF5A.
Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway
Authors: Shi Yixian , Li Yongjun , Huang Chenjie , Ying Lixiong , Xue Jihua , Wu Haicong , Chen Zhi , Yang Zhenggang
Published: April 2016

The population of hepatitis B combined with a number of metabolic disorders is increasing significantly. Resveratrol (RSV) has been used as a preclinical drug for the treatment of the metabolic disorders. However, the impact of RSV on HBV replication remains unknown. In this study, the HBV-expressing hepatocelluar carcinoma cell line and mouse model created by hydrodynamic injection of viral DNA were used. We found that RSV activates Sirt1, which in turn deacetylates PGC-1α and subsequently increases the transcriptional activity of PPARα, leading to the enhanced HBV transcription and replication in vitro and in vivo. In addition, we found that this pathway is also required for fasting-induced HBV transcription. Taken together, this study identifies that RSV enhances HBV transcription and replication especially acting on the core promoter, which depends on Sirt1-PGC-1α-PPARα pathway. We conclude that RSV may exacerbate the progression of hepatitis B and that patients with hepatitis B infection should be cautious taking RSV as a dietary supplement.
Autophagy inhibition of hsa-miR-19a-3p/19b-3p by targeting TGF-β R II during TGF-β1-induced fibrogenesis in human cardiac fibroblasts
Authors: Zou Meijuan , Wang Fang , Gao Rui , Wu Jingjing , Ou Yingwei , Chen Xuguan , Wang Tongshan , Zhou Xin , Zhu Wei , Li Ping , Qi Lian-Wen , Jiang Ting , Wang Weiwei , Li Chunyu , Chen Jun , He Qifang , Chen Yan
Published: April 2016

Transforming growth factor-β1 (TGF-β1) plays an important role on fibrogenesis in heart disease. MicroRNAs have exhibited as crucial regulators of cardiac homeostasis and remodeling in various heart diseases. MiR-19a-3p/19b-3p expresses with low levels in the plasma of heart failure patients. The purpose of our study is to determine the role of MiR-19a-3p/19b-3p in regulating autophagy-mediated fibrosis of human cardiac fibroblasts. We elucidate our hypothesis in clinical samples and human cardiac fibroblasts (HCF) to provide valuable basic information. TGF-β1 promotes collagen I α2 and fibronectin synthesis in HCF and that is paralleled by autophagic activation in these cells. Pharmacological inhibition of autophagy by 3-methyladenine decreases the fibrotic response, while autophagy induction of rapamycin increases the response. BECN1 knockdown and Atg5 over-expression either inhibits or enhances the fibrotic effect of TGF-β1 in experimental HCF. Furthermore, miR-19a-3p/19b-3p mimics inhibit epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) prodution and invasion of HCF. Functional studies suggest that miR-19a-3p/19b-3p inhibits autophagy of HCF through targeting TGF-β R II mRNA. Moreover, enhancement of autophagy rescues inhibition effect of miR-19a-3p/19b-3p on Smad 2 and Akt phosphorylation through TGF-β R II signaling. Our study uncovers a novel mechanism that miR-19a-3p/19b-3p inhibits autophagy-mediated fibrogenesis by targeting TGF-β R II.
LINE-1-like retrotransposons contribute to RNA-based gene duplication in dicots
Authors: Zhu Zhenglin , Tan Shengjun , Zhang Yaqiong , Zhang Yong E.
Published: April 2016

RNA-based duplicated genes or functional retrocopies (retrogenes) are known to drive phenotypic evolution. Retrogenes emerge via retroposition, which is mainly mediated by long interspersed nuclear element 1 (LINE-1 or L1) retrotransposons in mammals. By contrast, long terminal repeat (LTR) retrotransposons appear to be the major player in plants, although an L1-like mechanism has also been hypothesized to be involved in retroposition. We tested this hypothesis by searching for young retrocopies, as these still retain the sequence features associated with the underlying retroposition mechanism. Specifically, we identified polymorphic retrocopies (retroCNVs) by analyzing public Arabidopsis (Arabidopsis thaliana) resequencing data. Furthermore, we searched for recently originated retrocopies encoded by the reference genome of Arabidopsis and Manihot esculenta. Across these two datasets, we found cases with L1-like hallmarks, namely, the expected target site sequence, a polyA tail and target site duplications. Such data suggest that an L1-like mechanism could operate in plants, especially dicots.
Centennial-scale solar forcing of the South American Monsoon System recorded in stalagmites
Authors: Novello Valdir F. , Vuille Mathias , Cruz Francisco W. , Stríkis Nicolás M. , de Paula Marcos Saito , Edwards R. Lawrence , Cheng Hai , Karmann Ivo , Jaqueto Plínio F. , Trindade Ricardo I. F. , Hartmann Gelvam A. , Moquet Jean S.
Published: April 2016

The South American Monsoon System (SAMS) is generally considered to be highly sensitive to Northern Hemisphere (NH) temperature variations on multi-centennial timescales. The direct influence of solar forcing on moisture convergence in global monsoon systems on the other hand, while well explored in modeling studies, has hitherto not been documented in proxy data from the SAMS region. Hence little is known about the sensitivity of the SAMS to solar forcing over the past millennium and how it might compete or constructively interfere with NH temperature variations that occurred primarily in response to volcanic forcing. Here we present a new annually-resolved oxygen isotope record from a 1500-year long stalagmite recording past changes in precipitation in the hitherto unsampled core region of the SAMS. This record details how solar variability consistently modulated the strength of the SAMS on centennial time scales during the past 1500 years. Solar forcing, besides the previously recognized influence from NH temperature changes and associated Intertropical Convergence Zone (ITCZ) shifts, appears as a major driver affecting SAMS intensity at centennial time scales.
In situ 3D topographic and shape analysis by synchrotron radiation X-ray microtomography for crystal form identification in polymorphic mixtures
Authors: Yin Xian-Zhen , Xiao Ti-Qiao , Nangia Ashwini , Yang Shuo , Lu Xiao-Long , Li Hai-Yan , Shao Qun , He You , York Peter , Zhang Ji-Wen
Published: April 2016

Polymorphism denotes the existence of more than one crystal structure of a substance and great practical and theoretical interest for the chemical and pharmaceutical industries. In many cases, it is challenging to produce a pure crystal form and establish a sensitive detection method for the identification of crystal form in a mixture of polymorphs. In this study, an accurate and sensitive method based on synchrotron radiation X-ray computed microtomography (SR-μCT) was devised to identify the polymorphs of clopidogrel bisulphate (CLP). After 3D reconstruction, crystal particles were extracted and dozens of structural parameters were calculated. Whilst, the particle shapes of the two crystal forms were all irregular, the surface of CLP II was found to be rougher than CLP I. In order to classify the crystal form based on the quantitative morphological property of particles, Volume Bias Percentage based on Surface Smoothing (VBP) was defined and a new method based on VBP was successfully developed, with a total matching rate of 99.91% for 4544 particles and a lowest detectable limit of 1%. More important for the mixtures in solid pharmaceutical formulations, the interference of excipients can be avoided, a feature cannot achieved by other available analytical methods.
Radiation Resistant Vanadium-Graphene Nanolayered Composite
Authors: Kim Youbin , Baek Jinwook , Kim Sunghwan , Kim Sangmin , Ryu Seunghwa , Jeon Seokwoo , Han Seung Min
Published: April 2016

Ultra high strength V-graphene nanolayers were developed for the first time that was demonstrated to have an excellent radiation tolerance as revealed by the He+ irradiation study. Radiation induced hardening, evaluated via nanopillar compressions before and after He+ irradiation, is significantly reduced with the inclusion of graphene layers; the flow stresses of V-graphene nanolayers with 110 nm repeat layer spacing showed an increase of 25% while pure V showed an increase of 88% after He+ dosage of 13.5 dpa. The molecular dynamics simulations confirmed that the graphene interface can spontaneously absorb the nearby crystalline defects that are produced from a collision cascade, thereby enhancing the lifetime of the V-graphene nanolayers via this self-healing effect. In addition, the impermeability of He gas through the graphene resulted in suppression of He bubble agglomerations that in turn reduced embrittlement. In-situ SEM compression also showed the ability of graphene to hinder crack propagation that suppressed the failure.
Antiferromagnetic Skyrmion: Stability, Creation and Manipulation
Authors: Zhang Xichao , Zhou Yan , Ezawa Motohiko
Published: April 2016

Magnetic skyrmions are particle-like topological excitations in ferromagnets, which have the topo-logical number Q = ± 1 and hence show the skyrmion Hall effect (SkHE) due to the Magnus force effect originating from the topology. Here, we propose the counterpart of the magnetic skyrmion in the antiferromagnetic (AFM) system, that is, the AFM skyrmion, which is topologically protected but without showing the SkHE. Two approaches for creating the AFM skyrmion have been described based on micromagnetic lattice simulations: (i) by injecting a vertical spin-polarized current to a nanodisk with the AFM ground state; (ii) by converting an AFM domain-wall pair in a nanowire junction. It is demonstrated that the AFM skyrmion, driven by the spin-polarized current, can move straightly over long distance, benefiting from the absence of the SkHE. Our results will open a new strategy on designing the novel spintronic devices based on AFM materials.