bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Representativeness of Primary Electorates
Authors: Sides John , Tausanovitch Chris , Vavreck Lynn , Warshaw Christopher
Published: March 2018

Primary voters are frequently characterized as an ideologically extreme subset of their party, and thus partially responsible for party polarization in government. This study uses a combination of administrative records on primary turnout and five recent surveys from 2008–14 to show that primary voters have similar demographic attributes and policy attitudes as rank-and-file voters in their party. These similarities do not vary according to the openness of the primary. These results suggest that the composition of primary electorates does not exert a polarizing effect above what might arise from voters in the party as a whole.
The role of metalloproteases inLeishmaniaspecies infection in the New World: a systematic review
Authors: Murase Letícia Sayuri , de Souza João Vítor Perez , de Lima Neto Quirino Alves , de Mello Tatiane França Perles , Cardoso Bruna Muller , Lera-Nonose Daniele Stéfanie Sara Lopes , Teixeira Jorge Juarez Vieira , Lonardoni Maria Valdrinez Campana , Demarchi Izabel Galhardo
Published: March 2018

This is a systematic review on the role of metalloproteases in the pathogenicity of the American tegumentary leishmaniasis (ATL) caused by New World Leishmania species. The review followed the PRISMA method, searching for articles in PubMed, EMBASE, LILACS and ISI Web of Science, by employing the following terms: ‘leishmaniasis’, ‘cutaneous leishmaniasis’, ‘mucocutaneous leishmaniasis’, ‘diffuse cutaneous leishmaniasis’, ‘Leishmania’ and ‘metalloproteases’. GP63 of New WorldLeishmaniaspecies is a parasite metalloproteases involved in the degradation and cleavage of many biological molecules as kappa-B nuclear factor, fibronectin, tyrosine phosphatases. GP63 is capable of inhibiting the activity of the complement system and reduces the host's immune functions, allowing the survival of the parasite and its dissemination. High serological/tissue levels of host matrix metalloproteases (MMP)-9 have been associated with tissue damage during the infection, while high transcriptional levels of MMP-2 related with a satisfactory response to treatment. Host MMPs serological and tissue levels have been investigated using Western Blot, zymography, and Real Time polymerase chain reaction. GP63 detection characterizes species and virulence in promastigotes isolated from lesions samples using techniques mentioned previously. The monitoring of host MMPs levels and GP63 in Leishmania isolated from host samples could be used on the laboratory routine to predict the prognostic and treatment efficacy of ATL.
Proximity to parasites reduces host fitness independent of infection in a Drosophila–Macrocheles system
Authors: Horn Collin J. , Luong Lien T.
Published: March 2018

Parasites are known to have direct negative effects on host fitness; however, the indirect effects of parasitism on host fitness sans infection are less well understood. Hosts undergo behavioural and physiological changes when in proximity to parasites. Yet, there is little experimental evidence showing that these changes lead to long-term decreases in host fitness. We aimed to determine if parasite exposure affects host fitness independent of contact, because current approaches to parasite ecology may underestimate the effect of parasites on host populations. We assayed the longevity and reproductive output of Drosophila nigrospiracula exposed or not exposed to ectoparasitic Macrocheles subbadius. In order to preclude contact and infection, mites and flies were permanently separated with a mesh screen. Exposed flies had shorter lives and lower fecundity relative to unexposed flies. Recent work in parasite ecology has argued that parasite–host systems show similar processes as predator–prey systems. Our findings mirror the non-consumptive effects observed in predator–prey systems, in which prey species suffer reduced fitness even if they never come into direct contact with predators. Our results support the perspective that there are analogous effects in parasite–host systems, and suggest new directions for research in both parasite ecology and the ecology of fear.
The risk of developing major depression among individuals with subthreshold depression: a systematic review and meta-analysis of longitudinal cohort studies
Authors: Lee Y. Y. , Stockings E. A. , Harris M. G. , Doi S. A. R. , Page I. S. , Davidson S. K. , Barendregt J. J.
Published: March 2018

Background

Studies have consistently shown that subthreshold depression is associated with an increased risk of developing major depression. However, no study has yet calculated a pooled estimate that quantifies the magnitude of this risk across multiple studies.

Methods

We conducted a systematic review to identify longitudinal cohort studies containing data on the association between subthreshold depression and future major depression. A baseline meta-analysis was conducted using the inverse variance heterogeneity method to calculate the incidence rate ratio (IRR) of major depression among people with subthreshold depression relative to non-depressed controls. Subgroup analyses were conducted to investigate whether IRR estimates differed between studies categorised by age group or sample type. Sensitivity analyses were also conducted to test the robustness of baseline results to several sources of study heterogeneity, such as the case definition for subthreshold depression.

Results

Data from 16 studies (n= 67 318) revealed that people with subthreshold depression had an increased risk of developing major depression (IRR = 1.95, 95% confidence interval 1.28–2.97). Subgroup analyses estimated similar IRRs for different age groups (youth, adults and the elderly) and sample types (community-based and primary care). Sensitivity analyses demonstrated that baseline results were robust to different sources of study heterogeneity.

Conclusion

The results of this study support the scaling up of effective indicated prevention interventions for people with subthreshold depression, regardless of age group or setting.
Mobilising alternative futures: generational accounting and the fiscal politics of ageing in Australia
Authors: SPIES-BUTCHER BEN , STEBBING ADAM
Published: March 2018

Economists typically argue population ageing generates fiscal pressures by restricting the tax base while increasing demands for social spending. Alongside other economic pressures associated with neoliberalism, this dynamic contributes to a politics of ‘enduring austerity’ that limits governments’ fiscal discretion. The politics of population ageing reflects modelling techniques, such as generational accounting (GA), which, anticipating future deficits, create demands for policy action today to address projected intergenerational inequalities. Taking Australia as a case study, this paper explores the politics of GA in public budgetary processes. While existing critiques reject GA by arguing it relies on ‘apocalyptic’ or unreliable demography, we focus on a different kind of contestation, which applies the techniques and even the categories of GA to frame different problems and promote different solutions. We identify three sites of partisan contest that refocus fiscal modelling: including the tax side of the budget equation; comparing the cost of public provision to public subsidies for private programmes; and including the costs of environmental damage. At each site, the future-orientated logic of GA is mobilised to contest the policy implications of austerity. This complicates analysis that financialisation and neoliberalism necessarily ‘de-politicise’ policy by removing state discretion. Instead, we identify an increasingly important, if technocratic, form of political contestation that offers the possibility to promote more egalitarian responses to population ageing.
Evaluation of measles and rubella integrated surveillance system in Apulia region, Italy, 3 years after its introduction
Authors: Turiac I. A. , Fortunato F. , Cappelli M. G. , Morea A. , Chironna M. , Prato Rosa , Martinelli D.
Published: March 2018

This study aimed at evaluating the integrated measles and rubella surveillance system (IMRSS) in Apulia region, Italy, from its introduction in 2013 to 30 June 2016. Measles and rubella case reports were extracted from IMRSS. We estimated system sensitivity at the level of case reporting, using the capture–recapture method for three data sources. Data quality was described as the completeness of variables and timeliness of notification as the median-time interval from symptoms onset to initial alert. The proportion of suspected cases with laboratory investigation, the rate of discarded cases and the origin of infection were also computed. A total of 127 measles and four rubella suspected cases were reported to IMRSS and 82 were laboratory confirmed. Focusing our analysis on measles, IMRSS sensitivity was 82% (95% CI: 75–87). Completeness was >98% for mandatory variables and 57% for ‘genotyping’. The median-time interval from symptoms onset to initial alert was 4.5 days, with a timeliness of notification of 33% (41 cases reported ⩽48 h). The proportion of laboratory investigation was 87%. The rate of discarded cases was 0.1 per 100 000 inhabitants per year. The origin of infection was identified for 85% of cases. It is concluded that IMRSS provides good quality data and has good sensitivity; still efforts should be made to improve the completeness of laboratory-related variables, timeliness and to increase the rate of discarded cases.
Foundations of dependent interoperability
Authors: DAGAND PIERRE-ÉVARISTE , TABAREAU NICOLAS , TANTER ÉRIC
Published: March 2018

Full-spectrum dependent types promise to enable the development of correct-by-construction software. However, even certified software needs to interact with simply-typed or untyped programs, be it to perform system calls, or to use legacy libraries. Trading static guarantees for runtime checks, thedependent interoperabilityframework provides a mechanism by which simply-typed values can safely be coerced to dependent types and, conversely, dependently-typed programs can defensively be exported to a simply-typed application. In this article, we give a semantic account of dependent interoperability. Our presentation relies on and is guided by a pervading notion of type equivalence, whose importance has been emphasized in recent work on homotopy type theory. Specifically, we develop the notions oftype-theoretic partial Galois connectionsas a key foundation for dependent interoperability, which accounts for the partiality of the coercions between types. We explore the applicability of both type-theoretic Galois connections and anticonnections in the setting of dependent interoperability. A partial Galois connection enforces a translation of dependent types to runtime checks that are both sound and complete with respect to the invariants encoded by dependent types. Conversely, picking an anticonnection instead lets us induce weaker, sound conditions that can amount to more efficient runtime checks.

Our framework is developed in Coq; it is thus constructive and verified in the strictest sense of the terms. Using our library, users can specify domain-specific partial connections between data structures. Our library then takes care of the (sometimes, heavy) lifting that leads to interoperable programs. It thus becomes possible, as we shall illustrate, to internalize and hand-tune the extraction of dependently-typed programs to interoperable OCaml programs within Coq itself.
A Descriptive Analysis of Care Provided by Law Enforcement Prior to EMS Arrival in the United States
Authors: Klassen Aaron B. , Core S. Brent , Lohse Christine M. , Sztajnkrycer Matthew D.
Published: March 2018

Study Objectives

Law enforcement is increasingly viewed as a key component in the out-of-hospital chain of survival, with expanded roles in cardiac arrest, narcotic overdose, and traumatic bleeding. Little is known about the nature of care provided by law enforcement prior to the arrival of Emergency Medical Services (EMS) assets. The purpose of the current study was to perform a descriptive analysis of events reported to a national EMS database.

Methods

This study was a descriptive analysis of the 2014 National Emergency Medical Services Information System (NEMSIS) public release research data set, containing EMS emergency response data from 41 states. Code E09_02 1200 specifically identifies care provided by law enforcement prior to EMS arrival.

Results

A total of 25,835,729 unique events were reported. Of events in which pre-arrival care was documented, 2.0% received prior aid by law enforcement. Patients receiving law enforcement care prior to EMS arrival were more likely to be younger (52.8 [SD=23.3] years versus 58.7 [SD=23.3] years), male (54.8% versus 46.7%), and white (80.3% versus 77.5%). Basic Life Support (BLS) EMS response was twice as likely in patients receiving prior aid by law enforcement. Multiple-casualty incidents were five times more likely with prior aid by law enforcement. Compared with prior aid by other services, law enforcement pre-arrival care was more likely with motor vehicle accidents, firearm assaults, knife assaults, blunt assaults, and drug overdoses, and less likely at falls and childbirths. Cardiac arrest was significantly more common in patients receiving prior aid by law enforcement (16.5% versus 2.6%). Tourniquet application and naloxone administration were more common in the law enforcement prior aid group.

Conclusion

Where noted, law enforcement pre-arrival care occurs in 2.0% of EMS patient encounters. The majority of cases involve cardiac arrest, motor vehicle accidents, and assaults. Better understanding of the nature of law enforcement care is required in order to identify potential barriers to care and to develop appropriate training and policy recommendations.

KlassenAB, CoreSB, LohseCM, SztajnkrycerMD. A descriptive analysis of care provided by law enforcement prior to EMS arrival in the United States. Prehosp Disaster Med. 2018;33(2):165–170.
Genetic differences in macro-element mineral concentrations among 52 historically important tomato varieties
Authors: Labate Joanne A. , Breksa Andrew P. , Robertson Larry D. , King Benjamin A. , King Darwin E.
Published: March 2018

Tomato (Solanum lycopersicum) fruit quality and yield are highly dependent on adequate uptake of nutrients. Potassium, magnesium and calcium are essential elements that influence fruit quality traits such as colour, uniformity of ripening, hollow fruit, fruit shape, firmness and acidity. Sodium is not an essential element for tomato and can detrimentally compete with the absorption of potassium and calcium. Daily intakes of potassium, magnesium and calcium in human diets are typically below healthful levels, while sodium intake is often excessive. The objective of this study was to compare 52 diverse commercially important varieties of tomato for concentrations of potassium, magnesium, calcium and sodium in fruits. The tomatoes were produced in replicated plots in Geneva, NY in 2010 and 2011. Multiple fruits per plot were harvested vine-ripe, homogenized and assayed for cations. Analysis of variance showed significant differences among the 52 varieties for all four traits, i.e. cation concentrations (df = 51, P < 0.0001–0.0034) and no significant differences between years for any trait (df = 1, P = 0.3432–0.6770). Factor analysis showed a strong interrelationship between potassium and magnesium that was independent of calcium and sodium. Potassium and magnesium were highly significantly correlated with each other (r = 0.64, P < 0.0001). No other correlations between pairs of traits were observed. Results supported a genetic basis for potassium, magnesium, calcium and sodium concentrations that was consistent across environments (i.e. years). Results can contribute to the development of cultivars with favourable cation profiles in terms of human health and fruit quality.
Institutions, rule-following and conditional reasoning
Authors: HÉDOIN CYRIL
Published: March 2018

This paper is a contribution to the advancement of a naturalistic social ontology. Individuals participate in an institutionalized practice by following rules. In this perspective, I show that the nature, the stability, and the dynamics of any institution depend on how people reason about states of affairs that do not occur. That means that counterfactual reasoning is essential in the working of institutions. I present arguments for the importance of counterfactuals as well as a game-theoretic framework to account for them. Since the role of counterfactuals does not directly transpire in people's behavior, the whole discussion can be seen as a broad argument against behaviorism in philosophy and the social sciences.
New Maps Highlight Antarctica’s Flowing Ice
Authors: Cartier Kimberly
Published: March 2018

The maps focus on surface ice velocity, showing how Antarctica’s frozen surface changed over a 7-year period.
Predator-secreted sulfolipids induce defensive responses in C. elegans
Authors: Liu Zheng , Kariya Maro J. , Chute Christopher D. , Pribadi Amy K. , Leinwand Sarah G. , Tong Ada , Curran Kevin P. , Bose Neelanjan , Schroeder Frank C. , Srinivasan Jagan , Chalasani Sreekanth H.
Published: March 2018

Animals respond to predators by altering their behavior and physiological states, but the underlying signaling mechanisms are poorly understood. Using the interactions between Caenorhabditis elegans and its predator, Pristionchus pacificus, we show that neuronal perception by C. elegans of a predator-specific molecular signature induces instantaneous escape behavior and a prolonged reduction in oviposition. Chemical analysis revealed this predator-specific signature to consist of a class of sulfolipids, produced by a biochemical pathway required for developing predacious behavior and specifically induced by starvation. These sulfolipids are detected by four pairs of C. elegans amphid sensory neurons that act redundantly and recruit cyclic nucleotide-gated (CNG) or transient receptor potential (TRP) channels to drive both escape and reduced oviposition. Functional homology of the delineated signaling pathways and abolishment of predator-evoked C. elegans responses by the anti-anxiety drug sertraline suggests a likely conserved or convergent strategy for managing predator threats.
Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells
Authors: Huels D. J. , Bruens L. , Hodder M. C. , Cammareri P. , Campbell A. D. , Ridgway R. A. , Gay D. M. , Solar-Abboud M. , Faller W. J. , Nixon C. , Zeiger L. B. , McLaughlin M. E. , Morrissey E. , Winton D. J. , Snippert H. J. , van Rheenen J. , Sansom O. J.
Published: March 2018

Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+ stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that crypts become rapidly derived from a single stem cell. Stem cells located further from the base are lost and the pool of competing stem cells is reduced. We tested whether this loss of stem cell competition would modify tumorigenesis. Reduction of Wnt ligand secretion accelerates fixation of Apc-deficient cells within the crypt leading to accelerated tumorigenesis. Therefore, ligand-based Wnt signalling influences the number of stem cells, fixation speed of Apc mutations and the speed and likelihood of adenoma formation.
Pre-Columbian earth-builders settled along the entire southern rim of the Amazon
Authors: de Souza Jonas Gregorio , Schaan Denise Pahl , Robinson Mark , Barbosa Antonia Damasceno , Aragão Luiz E. O. C. , Marimon Ben Hur , Marimon Beatriz Schwantes , da Silva Izaias Brasil , Khan Salman Saeed , Nakahara Francisco Ruji , Iriarte José
Published: March 2018

The discovery of large geometrical earthworks in interfluvial settings of southern Amazonia has challenged the idea that Pre-Columbian populations were concentrated along the major floodplains. However, a spatial gap in the archaeological record of the Amazon has limited the assessment of the territorial extent of earth-builders. Here, we report the discovery of Pre-Columbian ditched enclosures in the Tapajós headwaters. The results show that an 1800 km stretch of southern Amazonia was occupied by earth-building cultures living in fortified villages ~Cal AD 1250–1500. We model earthwork distribution in this broad region using recorded sites, with environmental and terrain variables as predictors, estimating that earthworks will be found over ~400,000 km2of southern Amazonia. We conclude that the interfluves and minor tributaries of southern Amazonia sustained high population densities, calling for a re-evaluation of the role of this region for Pre-Columbian cultural developments and environmental impact.
Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus
Authors: Liu Junli , Huang Xinfang , Hao Shumeng , Wang Yan , Liu Manman , Xu Jing , Zhang Xingli , Yu Tao , Gan Shucheng , Dai Dongfang , Luo Xuan , Lu Qingyan , Mao Chaoming , Zhang Yanyun , Shen Nan , Li Bin , Huang Mingzhu , Zhu Xiaodong , Jin Jin , Cheng Xuhong , Sun Shao-Cong , Xiao Yichuan
Published: March 2018

Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-κB signaling. Mechanically, Peli1 functions as an E3 ligase to associate with NF-κB inducing kinase (NIK) and mediates NIK Lys48 ubiquitination and degradation. Overexpression of Peli1 inhibits noncanonical NF-κB activation and alleviates lupus-like disease. In humans, PELI1 levels negatively correlate with disease severity in SLE patients. Our findings establish Peli1 as a negative regulator of the noncanonical NF-κB pathway in the context of restraining the pathogenesis of lupus-like disease.
Biomimetic artificial organelles with in vitro and in vivo activity triggered by reduction in microenvironment
Authors: Einfalt T. , Witzigmann D. , Edlinger C. , Sieber S. , Goers R. , Najer A. , Spulber M. , Onaca-Fischer O. , Huwyler J. , Palivan C. G.
Published: March 2018

Despite tremendous efforts to develop stimuli-responsive enzyme delivery systems, their efficacy has been mostly limited to in vitro applications. Here we introduce, by using an approach of combining biomolecules with artificial compartments, a biomimetic strategy to create artificial organelles (AOs) as cellular implants, with endogenous stimuli-triggered enzymatic activity. AOs are produced by inserting protein gates in the membrane of polymersomes containing horseradish peroxidase enzymes selected as a model for natures own enzymes involved in the redox homoeostasis. The inserted protein gates are engineered by attaching molecular caps to genetically modified channel porins in order to induce redox-responsive control of the molecular flow through the membrane. AOs preserve their structure and are activated by intracellular glutathione levels in vitro. Importantly, our biomimetic AOs are functional in vivo in zebrafish embryos, which demonstrates the feasibility of using AOs as cellular implants in living organisms. This opens new perspectives for patient-oriented protein therapy.
Chromate replacement: what does the future hold?
Authors: Gharbi Oumaïma , Thomas Sebastian , Smith Craig , Birbilis Nick
Published: March 2018

The ubiquitous use of chromium and its derivatives as corrosion preventative compounds accelerated rapidly after the second industrial revolution, with such compounds now integral to modern society. However, the detrimental impact of chromium compounds on the environment and human health has prompted the need to revisit the majority of current industrial corrosion protection measures. This review retraces the origins of chromium replacement motivations, introducing the various legislative actions aimed at diminishing the use of chromium compounds, and critically reviews alternative corrosion preventative technologies developed in the recent decades to now. The review, herein, is intended for a broad audience in order to provide a concise update to an increasingly timely issue.
Altered DNA methylation associated with a translocation linked to major mental illness
Authors: McCartney Daniel L. , Walker Rosie M. , Morris Stewart W. , Anderson Susan M. , Duff Barbara J. , Marioni Riccardo E. , Millar J. Kirsty , McCarthy Shane E. , Ryan Niamh M. , Lawrie Stephen M. , Watson Andrew R. , Blackwood Douglas H. R. , Thomson Pippa A. , McIntosh Andrew M. , McCombie W. Richard , Porteous David J. , Evans Kathryn L.
Published: March 2018

Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, CA). We found significant differences in DNA methylation when translocation carriers (n = 17) were compared to related non-carriers (n = 24) at 13 loci. All but one of the 13 significant differentially methylated positions (DMPs) mapped to the regions surrounding the translocation breakpoints. Methylation levels of five DMPs were associated with genotype at SNPs in linkage disequilibrium with the translocation. Two of the five genes harbouring significant DMPs,DISC1andDUSP10, have been previously shown to be differentially methylated in schizophrenia. Gene Ontology analysis revealed enrichment for terms relating to neuronal function and neurodevelopment among the genes harbouring the most significant DMPs. Differentially methylated region (DMR) analysis highlighted a number of genes from the MHC region, which has been implicated in psychiatric illness previously through genetic studies. We show that inheritance of a translocation linked to major mental illness is associated with differential DNA methylation at loci implicated in neuronal development/function and in psychiatric illness. As genomic rearrangements are over-represented in individuals with psychiatric illness, such analyses may be valuable more widely in the study of these conditions.
Analysis of microRNA and Gene Expression Profiles in Alzheimer’s Disease: A Meta-Analysis Approach
Authors: Moradifard Shirin , Hoseinbeyki Moslem , Ganji Shahla Mohammad , Minuchehr Zarrin
Published: March 2018

Understanding the molecular mechanisms underlying Alzheimer’s disease (AD) is necessary for the diagnosis and treatment of this neurodegenerative disorder. It is therefore important to detect the most important genes and miRNAs, which are associated with molecular events, and studying their interactions for recognition of AD mechanisms. Here we focus on the genes and miRNAs expression profile, which we have detected the miRNA target genes involved in AD. These are the most quintessential to find the most important miRNA, to target genes and their important pathways. A total of 179 differentially expressed miRNAs (DEmiRs) and 1404 differentially expressed genes (DEGs) were obtained from a comprehensive meta-analysis. Also, regions specific genes with their molecular function in AD have been demonstrated. We then focused on miRNAs which regulated most genes in AD, alongside we analyzed their pathways. The miRNA-30a-5p and miRNA-335 elicited a major function in AD after analyzing the regulatory network, we showed they were the most regulatory miRNAs in the AD. In conclusion, we demonstrated the most important genes, miRNAs, miRNA-mRNA interactions and their related pathways in AD using Bioinformatics methods. Accordingly, our defined genes and miRNAs could be used for future molecular studies in the context of AD.
Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy
Authors: Birtel Johannes , Eisenberger Tobias , Gliem Martin , Müller Philipp L. , Herrmann Philipp , Betz Christian , Zahnleiter Diana , Neuhaus Christine , Lenzner Steffen , Holz Frank G. , Mangold Elisabeth , Bolz Hanno J. , Charbel Issa Peter
Published: March 2018

Macular and cone/cone-rod dystrophies (MD/CCRD) demonstrate a broad genetic and phenotypic heterogeneity, with retinal alterations solely or predominantly involving the central retina. Targeted next-generation sequencing (NGS) is an efficient diagnostic tool for identifying mutations in patient with retinitis pigmentosa, which shows similar genetic heterogeneity. To detect the genetic causes of disease in patients with MD/CCRD, we implemented a two-tier procedure consisting of Sanger sequencing and targeted NGS including genes associated with clinically overlapping conditions. Disease-causing mutations were identified in 74% of 251 consecutive MD/CCRD patients (33% of the variants were novel). Mutations in ABCA4, PRPH2 and BEST1 accounted for 57% of disease cases. Further mutations were identified in CDHR1, GUCY2D, PROM1, CRX, GUCA1A, CERKL, MT-TL1, KIF11, RP1L1, MERTK, RDH5, CDH3, C1QTNF5, CRB1, JAG1, DRAM2, POC1B, NPHP1 and RPGR. We provide detailed illustrations of rare phenotypes, including autofluorescence and optical coherence tomography imaging. Targeted NGS also identified six potential novel genotype-phenotype correlations for FAM161A, INPP5E, MERTK, FBLN5, SEMA4A and IMPDH1. Clinical reassessment of genetically unsolved patients revealed subgroups with similar retinal phenotype, indicating a common molecular disease cause in each subgroup.
Accelerated seed dispersal along linear disturbances in the Canadian oil sands region
Authors: Roberts David , Ciuti Simone , Barber Quinn E. , Willier Caitlin , Nielsen Scott E.
Published: March 2018

Habitat fragmentation is typically seen as inhibiting movement via erosion in connectivity, although some patterns of early-phase disturbance, such as narrow linear disturbances in otherwise undisturbed forests, may actually facilitate the dispersal of certain species. Such features are common in Alberta’s oil sands region as legacies from seismic hydrocarbon exploration used to map oil reserves. Many of the ecological implications of these disturbances are unknown. Here, we investigate the effect of these forest dissections by experimentally testing dispersal patterns along seismic lines compared with adjacent forests using two proxy materials for wind-dispersed seeds, Typha latifolia seed and goose down feathers. We found that wind speeds were up to seven times higher and 95th percentile seed dispersal distances nearly four times farther on seismic lines compared with undisturbed forests and the corresponding effect of these features on seed dispersal distances can be substantial, potentially facilitating future changes in composition and ecological processes in boreal forests. This raises important considerations for native and invasive species, particularly in the context of climate change and the associated importance of seed movement and migration.
A Modular Microfluidic Device via Multimaterial 3D Printing for Emulsion Generation
Authors: Ji Qinglei , Zhang Jia Ming , Liu Ying , Li Xiying , Lv Pengyu , Jin Dongping , Duan Huiling
Published: March 2018

3D-printing (3DP) technology has been developing rapidly. However, limited studies on the contribution of 3DP technology, especially multimaterial 3DP technology, to droplet-microfluidics have been reported. In this paper, multimaterial 3D-printed devices for the pneumatic control of emulsion generation have been reported. A 3D coaxial flexible channel with other rigid structures has been designed and printed monolithically. Numerical and experimental studies have demonstrated that this flexible channel can be excited by the air pressure and then deform in a controllable way, which can provide the active control of droplet generation. Furthermore, a novel modular microfluidic device for double emulsion generation has been designed and fabricated, which consists of three modules: function module, T-junction module, and co-flow module. The function module can be replaced by (1) Single-inlet module, (2) Pneumatic Control Unit (PCU) module and (3) Dual-inlet module. Different modules can be easily assembled for different double emulsion production. By using the PCU module, double emulsions with different number of inner droplets have been successfully produced without complicated operation of flow rates of different phases. By using single and dual inlet module, various double emulsions with different number of encapsulated droplets or encapsulated droplets with different compositions have been successfully produced, respectively.
Frataxin overexpression in Müller cells protects retinal ganglion cells in a mouse model of ischemia/reperfusion injury in vivo
Authors: Schultz Rowena , Krug Melanie , Precht Michel , Wohl Stefanie G. , Witte Otto W. , Schmeer Christian
Published: March 2018

Müller cells are critical for retinal function and neuronal survival but can become detrimental in response to retinal ischemia and increased oxidative stress. Elevated oxidative stress increases expression of the mitochondrial enzyme frataxin in the retina, and its overexpression is neuroprotective after ischemia. Whether frataxin expression in Müller cells might improve their function and protect neurons after ischemia is unknown. The aim of this study was to evaluate the effect of frataxin overexpression in Müller cells on neuronal survival after retinal ischemia/reperfusion in the mouse in vivo. Retinal ischemia/reperfusion was induced in mice overexpressing frataxin in Müller cells by transient elevation of intraocular pressure. Retinal ganglion cells survival was determined 14 days after lesion. Expression of frataxin, antioxidant enzymes, growth factors and inflammation markers was determined with qRT-PCR, Western blotting and immunohistochemistry 24 hours after lesion. Following lesion, there was a 65% increase in the number of surviving RGCs in frataxin overexpressing mice. Improved survival was associated with increased expression of the antioxidant enzymes Gpx1 and Sod1 as well as the growth factors Cntf and Lif. Additionally, microglial activation was decreased in these mice. Therefore, support of Müller cell function constitutes a feasible approach to reduce neuronal degeneration after ischemia.
Self-assembling asymmetric peptide-dendrimer micelles – a platform for effective and versatile in vitro nucleic acid delivery
Authors: Kokil Ganesh R. , Veedu Rakesh N. , Le Bao Tri , Ramm Grant A. , Parekh Harendra S.
Published: March 2018

Despite advancements in the development of high generation cationic-dendrimer systems for delivery of nucleic acid-based therapeutics, commercially available chemical agents suffer from major drawbacks such as cytotoxicity while being laborious and costly to synthesize. To overcome the aforementioned limitations, low-generation cationic peptide asymmetric dendrimers with side arm lipid (cholic and decanoic acid) conjugation were designed, synthesized and systematically screened for their ability to self-assemble into micelles using dynamic light scattering. Cytotoxicity profiling revealed that our entire asymmetric peptide dendrimer library when trialled alone, or as asymmetric dendrimer micelle-nucleic acid complexes, were non-cytotoxic across a broad concentration range. Further, the delivery efficiency of asymmetric peptide dendrimers in H-4-II-E (rat hepatoma), H2K (mdx mouse myoblast), and DAOY (human medulloblastoma) cells demonstrated that cholic acid-conjugated asymmetric dendrimers possess far superior delivery efficiency when compared to the commercial standards, Lipofectamine 2000 or Lipofectin®.
Non-equilibrium synergistic effects in atmospheric pressure plasmas
Authors: Guo Heng , Zhang Xiao-Ning , Chen Jian , Li He-Ping , Ostrikov Kostya
Published: March 2018

Non-equilibrium is one of the important features of an atmospheric gas discharge plasma. It involves complicated physical-chemical processes and plays a key role in various actual plasma processing. In this report, a novel complete non-equilibrium model is developed to reveal the non-equilibrium synergistic effects for the atmospheric-pressure low-temperature plasmas (AP-LTPs). It combines a thermal-chemical non-equilibrium fluid model for the quasi-neutral plasma region and a simplified sheath model for the electrode sheath region. The free-burning argon arc is selected as a model system because both the electrical-thermal-chemical equilibrium and non-equilibrium regions are involved simultaneously in this arc plasma system. The modeling results indicate for the first time that it is the strong and synergistic interactions among the mass, momentum and energy transfer processes that determine the self-consistent non-equilibrium characteristics of the AP-LTPs. An energy transfer process related to the non-uniform spatial distributions of the electron-to-heavy-particle temperature ratio has also been discovered for the first time. It has a significant influence for self-consistently predicting the transition region between the “hot” and “cold” equilibrium regions of an AP-LTP system. The modeling results would provide an instructive guidance for predicting and possibly controlling the non-equilibrium particle-energy transportation process in various AP-LTPs in future.
Comparison of twelve liver functional reserve models for outcome prediction in patients with hepatocellular carcinoma undergoing surgical resection
Authors: Ho Shu-Yein , Liu Po-Hong , Hsu Chia-Yang , Hsia Cheng-Yuan , Su Chien-Wei , Lee Yun-Hsuan , Huang Yi-Hsiang , Lee Fa-Yauh , Hou Ming-Chih , Huo Teh-Ia
Published: March 2018

Various noninvasive liver functional reserve models have been proposed, but their prognostic ability in patients with hepatocellular carcinoma (HCC) is unclear. We aimed to investigate the performance of twelve noninvasive liver reserve models in HCC patients undergoing surgical resection. A total of 645 patients undergoing resection were prospectively identified and retrospectively analyzed. Tumor recurrence, overall survival, and independent prognostic factors were evaluated by the Cox proportional hazards model. Of the twelve models, the King’s score showed the highest homogeneity and lowest corrected Akaike information criterion (AICc) value, suggesting a better predictive ability for tumor recurrence. In multivariate Cox analysis, we confirmed that King’s score, tumor size and serum alpha-fetoprotein level were independent predictors associated with recurrence. In survival prediction, albumin-bilirubin (ALBI) revealed the highest homogeneity and lowest value among twelve invasive models, indicating a better prognostic performance. In the Cox model, ALBI grade, tumor burden, alpha-fetoprotein, vascular invasion, diabetes mellitus and performance status were independent predictors linked with overall survival. In summary, the currently used liver function models have differential predictive ability for HCC patients undergoing surgical resection. The King’s score is a feasible tool to predict tumor recurrence, whereas ALBI grade is a more robust model for prognostic prediction.
Evidence from EXAFS for Different Ta/Ti Site Occupancy in High Critical Current Density Nb3Sn Superconductor Wires
Authors: Heald Steve M. , Tarantini Chiara , Lee Peter J. , Brown Michael D. , Sung ZuHawn , Ghosh Arup K. , Larbalestier David C.
Published: March 2018

To meet critical current density, J
c
, targets for the Future Circular Collider (FCC), the planned replacement for the Large Hadron Collider (LHC), the high field performance of Nb3Sn must be improved, but champion J
c
values have remained static for the last 10 years. Making the A15 phase stoichiometric and enhancing the upper critical field H
c2
by Ti or Ta dopants are the standard strategies for enhancing high field performance but detailed recent studies show that even the best modern wires have broad composition ranges. To assess whether further improvement might be possible, we employed Extended X-ray Absorption Fine Structure (EXAFS) to determine the lattice site location of dopants in modern high-performance Nb3Sn strands with J
c
values amongst the best so far achieved. Although Ti and Ta primarily occupy the Nb sites in the A15 structure, we also find significant Ta occupancy on the Sn site. These findings indicate that the best performing Ti-doped stand is strongly sub-stoichiometric in Sn and that antisite disorder likely explains its high average H
c2
behavior. These new results suggest an important role for dopant and antisite disorder in minimizing superconducting property distributions and maximizing high field J
c
properties.
Mechanisms underlying the lack of endogenous processing and CLIP-mediated binding of the invariant chain by HLA-DP84Gly
Authors: Anczurowski Mark , Yamashita Yuki , Nakatsugawa Munehide , Ochi Toshiki , Kagoya Yuki , Guo Tingxi , Wang Chung-Hsi , Rahman Muhammed A. , Saso Kayoko , Butler Marcus O. , Hirano Naoto
Published: March 2018

While the principles of classical antigen presentation via MHC class II are well-established, the mechanisms for the many routes of cross-presentation by which endogenous antigens become associated with class II molecules are not fully understood. We have recently demonstrated that the single amino acid polymorphism HLA-DPβ84Gly(DP84Gly) is critical to abrogate class II invariant chain associated peptide (CLIP) region-mediated binding of invariant chain (Ii) to DP, allowing endoplasmic reticulum (ER)-resident endogenous antigens to constitutively associate with DP84Glysuch as DP4. In this study, we demonstrate that both the CLIP and N-terminal non-CLIP Ii regions cooperatively generate an Ii conformation that cannot associate with DP84Glyvia the CLIP region. We also demonstrate the ability of DP4 to efficiently process and present antigens encoded in place of CLIP in a chimeric Ii, regardless of wild type Ii and HLA-DM expression. These data highlight the complex interplay between DP polymorphisms and the multiple Ii regions that cooperatively regulate this association, ultimately controlling the presentation of endogenous antigens on DP molecules. These results may also offer a mechanistic explanation for recent studies identifying the differential effects between DP84Glyand DP84Aspas clinically relevant in human disease.
Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study
Authors: Yadav Dharmendra K. , Kumar Surendra , Saloni  , Misra Sanjeev , Yadav Lalit , Teli Mahesh , Sharma Praveen , Chaudhary Sandeep , Kumar Naresh , Choi Eun Ha , Kim Hyung Sik , Kim Mi-hyun
Published: March 2018

SIRT6 and COX-2 are oncogenes target that promote the expression of proinflammatory and pro-survival proteins through a signaling pathway, which leads to increased survival and proliferation of tumor cells. However, COX-2 also suppresses skin tumorigenesis and their relationship with SIRT6, making it an interesting target for the discovery of drugs with anti-inflammatory and anti-cancer properties. Herein, we studied the interaction of thieno[3,2-c]pyran analogs and RONS species with SIRT6 and COX-2 through the use of molecular docking and molecular dynamic simulations. Molecular docking studies revealed the importance of hydrophobic and hydrophilic amino acid residues for the stability. The molecular dynamics study examined conformational changes in the enzymes caused by the binding of the substrates and how those changes affected the stability of the protein-drug complex. The average RMSD values of the backbone atoms in compounds 6 and 10 were calculated from 1000 ps to 10000 ps and were found to be 0.13 nm for both compounds. Similarly, the radius of gyration values for compounds 6 and 10 were found to be 1.87 ± 0.03 nm and 1.86 ± 0.02 nm, respectively. The work presented here, will be of great help in lead identification and optimization for early drug discovery.
The effects of crystalloid versus synthetic colloid in vitro on immune cells, co-cultured with mouse splenocytes
Authors: Lee Seung Hyun , Seo Eun-Hye , Park Hyun Jun , Oh Chung-Sik , Kim Cho Long , Park Sewon , Kim Seong-Hyop
Published: March 2018

This study assessed the effects of crystalloid versus synthetic colloid in vitro on immune cells co-cultured with mouse splenocytes. Mouse splenocytes were co-cultured with three different types of fluid: Plasma solution-A® (CJ HealthCare, Seoul, Korea; the crystalloid group); Tetraspan 6%® (B. Braun Medical, Melsungen, Germany; the Colloid-T group); and Volulyte 6%® (Fresenius Kabi, Bad Homburg vor dér-Höhe, Germany; Colloid-V group). To evaluate the acquired immune response, cluster of differentiation (CD) 4+ T cells and CD8+ T cells were measured. To evaluate the innate immune response, neutrophils were measured. The frequencies of CD4+ and CD8+ T cells did not differ significantly among the three groups on day 1 or 3. However, the frequencies of CD4+ and CD8+ T cells in the two synthetic colloid groups were significantly higher than those in the crystalloid group on day 7. On day 1, the frequency of neutrophils was significantly lower in the two synthetic colloid groups, compared with the crystalloid group. However, the values on the other days were similar among all three groups. In conclusion, crystalloid had a limited effect on the immune response; on the other hand, synthetic colloid increased the acquired immune response, although it temporarily inhibited the innate immune response.
Structural and magnetic properties of cobalt iron disulfide (CoxFe1−xS2) nanocrystals
Authors: Gabold Henrik , Luan Zhongyue , Paul Neelima , Opel Matthias , Müller-Buschbaum Peter , Law Matt , Paul Amitesh
Published: March 2018

We report on synthesis and investigation of nanocrystalline cobalt-iron-pyrites with an emphasis on nanocrystal structure, morphology and magnetic behavior. The nanocrystals (NCs) were 5–25 nm in diameter as characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). With an increase in Fe fraction, X-ray diffraction and small-angle-X-ray scattering (SAXS) showed a systematic decrease in lattice constant, primary grain/NC size (15 to 7 nm), and nanoparticle (NP) size (70 to 20 nm), respectively. The temperature dependence of the DC magnetization and AC susceptibility versus frequency revealed a number of magnetic phases in Co
x
Fe1−xS2. Samples with x = 1 and x = 0.875–0.625 showed evidence of superspin glass (SSG) behavior with embedded ferromagnetic (FM) clusters of NPs. For x = 0.5, samples retained their mixed phases, but showed superparamagnetic (SPM) behavior with antiferromagnetic clusters suppressing magnetic dipolar interactions. Below x = 0.5, the pyrites show increasing paramagnetic character. We construct a phase diagram, which can be understood in terms of competition between the various dipolar, exchange, inter- and intracluster interactions. Our results suggest that NC size and shape can be tuned to engineer spin-polarized ferromagnetism of n-doped iron pyrite.