bluuebunny/crossref_metadata_2025 huggingface dataset:
Significant data region identification and analysis using k‐means in large storage drive forensics
Authors: Bharadwaj Nitesh K. , Singh Upasna
Published: September 2018

The recent technological advancement with less implementation cost has completely changed the scenario of information being generated, stored, or manipulated digitally by using the storage devices. Today the criminal activities are directly or indirectly associated with the storage devices, thus it is now recognized as an essential evidence in court‐of‐law throughout the world. However, the massive capacities of modern storage devices significantly increase the time and effort required to preserve and analyze the evidence. This paper proposes a methodology based on the random sector sampling and k‐means clustering approaches to efficiently identify and evaluate the significant data regions instead of the entire storage drive. The random sampling and clustering methods efficiently reveal the unseen resident data pattern and intelligence about the regions of the drive which may be of investigator's interest. Experiments involving storage drives of various capacities demonstrate the efficacy of the methodology. Moreover, we generalize our discussion to represent that the extracted hidden patterns of storage drive data can assist an investigator in achieving the desired performance requirements.
The severity of psychiatric disorders
Authors: Zimmerman Mark , Morgan Theresa A. , Stanton Kasey
Published: September 2018

The issue of the severity of psychiatric disorders has great clinical importance. For example, severity influences decisions about level of care, and affects decisions to seek government assistance due to psychiatric disability. Controversy exists as to the efficacy of antidepressants across the spectrum of depression severity, and whether patients with severe depression should be preferentially treated with medication rather than psychotherapy. Measures of severity are used to evaluate outcome in treatment studies and may be used as meaningful endpoints in clinical practice. But, what does it mean to say that someone has a severe illness? Does severity refer to the number of symptoms a patient is experiencing? To the intensity of the symptoms? To symptom frequency or persistence? To the impact of symptoms on functioning or on quality of life? To the likelihood of the illness resulting in permanent disability or death? Putting aside the issue of how severity should be operationalized, another consideration is whether severity should be conceptualized similarly for all illnesses or be disorder specific. In this paper, we examine how severity is characterized in research and contemporary psychiatric diagnostic systems, with a special focus on depression and personality disorders. Our review shows that the DSM‐5 has defined the severity of various disorders in different ways, and that researchers have adopted a myriad of ways of defining severity for both depression and personality disorders, although the severity of the former was predominantly defined according to scores on symptom rating scales, whereas the severity of the latter was often linked with impairments in functioning. Because the functional impact of symptom‐defined disorders depends on factors extrinsic to those disorders, such as self‐efficacy, resilience, coping ability, social support, cultural and social expectations, as well as the responsibilities related to one's primary role function and the availability of others to assume those responsibilities, we argue that the severity of such disorders should be defined independently from functional impairment.
Psychological interventions to reduce positive symptoms in schizophrenia: systematic review and network meta‐analysis
Authors: Bighelli Irene , Salanti Georgia , Huhn Maximilian , Schneider‐Thoma Johannes , Krause Marc , Reitmeir Cornelia , Wallis Sofia , Schwermann Felicitas , Pitschel‐Walz Gabi , Barbui Corrado , Furukawa Toshi A. , Leucht Stefan
Published: September 2018

Psychological treatments are increasingly regarded as useful interventions for schizophrenia. However, a comprehensive evaluation of the available evidence is lacking and the benefit of psychological interventions for patients with current positive symptoms is still debated. The present study aimed to evaluate the efficacy, acceptability and tolerability of psychological treatments for positive symptoms of schizophrenia by applying a network meta‐analysis approach, that can integrate direct and indirect comparisons. We searched EMBASE, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Library, World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov for randomized controlled trials of psychological treatments for positive symptoms of schizophrenia, published up to January 10, 2018. We included studies on adults with a diagnosis of schizophrenia or a related disorder presenting positive symptoms. The primary outcome was change in positive symptoms measured with validated rating scales. We included 53 randomized controlled trials of seven psychological interventions, for a total of 4,068 participants receiving the psychological treatment as add‐on to antipsychotics. On average, patients were moderately ill at baseline. The network meta‐analysis showed that cognitive behavioural therapy (40 studies) reduced positive symptoms more than inactive control (standardized mean difference, SMD=−0.29; 95% CI: –0.55 to −0.03), treatment as usual (SMD=−0.30; 95% CI: –0.45 to −0.14) and supportive therapy (SMD=−0.47; 95% CI: –0.91 to −0.03). Cognitive behavioural therapy was associated with a higher dropout rate compared with treatment as usual (risk ratio, RR=0.74; 95% CI: 0.58 to 0.95). Confidence in the estimates ranged from moderate to very low. The other treatments contributed to the network with a lower number of studies. Results were overall consistent in sensitivity analyses controlling for several factors, including the role of researchers’ allegiance and blinding of outcome assessor. Cognitive behavior therapy seems to be effective on positive symptoms in moderately ill patients with schizophrenia, with effect sizes in the lower to medium range, depending on the control condition.
Treatment of Knee Meniscus Pathology: Rehabilitation, Surgery, and Orthobiologics
Authors: Chirichella Paul S. , Jow Steven , Iacono Stephen , Wey Hannah E. , Malanga Gerard A.
Published: September 2018

The meniscal tear treatment paradigm traditionally begins with conservative measures such as physical therapy and referral for operative management for persistent or mechanical symptoms. As a result, the partial meniscectomy is performed more than any other orthopedic procedure in the United States. This treatment paradigm has shifted because recent literature has supported the attempt to preserve or repair the meniscus whenever possible given its importance for the structural integrity of the knee joint and the risk of early osteoarthritis associated after meniscus excision. Choosing an appropriate management strategy depends on multiple factors such as patient demographics and location of the tear. Physical therapy remains a first‐line treatment for knee pain secondary to meniscus tear and should be pursued in the setting of acute and chronic knee pain. Furthermore, there is a growing amount of evidence showing that elderly patients with complex meniscus tears in the setting of degenerative arthritis should not undergo arthroscopic surgery. Direct meniscus repair remains an option in ideal patients who are young, healthy, and have tears near the more vascular periphery of the meniscus but it is not suitable for all patients. Use of orthobiologics such as platelet‐rich plasma and mesenchymal stem cells have shown promise in augmenting surgical repairs or as standalone treatments, although research for their use in meniscal tear management is limited.
Health Planning in 1960s Africa: International Health Organisations and the Post-Colonial State
Authors: Manton John , Gorsky Martin
Published: September 2018

This article explores the programme of national health planning carried out in the 1960s in West and Central Africa by the World Health Organization (WHO), in collaboration with the United States Agency for International Development (USAID). Health plans were intended as integral aspects of economic development planning in five newly independent countries: Gabon, Liberia, Mali, Niger and Sierra Leone. We begin by showing that this episode is treated only superficially in the existing WHO historiography, then introduce some relevant critical literature on the history of development planning. Next we outline the context for health planning, noting: the opportunities which independence from colonial control offered to international development agencies; the WHO’s limited capacity in Africa; and its preliminary efforts to avoid imposing Western values or partisan views of health system organisation. Our analysis of the plans themselves suggests they lacked the necessary administrative and statistical capacity properly to gauge local needs, while the absence of significant financial resources meant that they proposed little more than augmentation of existing structures. By the late 1960s optimism gave way to disappointment as it became apparent that implementation had been minimal. We describe the ensuing conflict within WHO over programme evaluation and ongoing expenditure, which exposed differences of opinion between African and American officials over approaches to international health aid. We conclude with a discussion of how the plans set in train longer processes of development planning, and, perhaps less desirably, gave bureaucratic shape to the post-colonial state.
Bank Capital and Lending: Evidence from Syndicated Loans
Authors: Chu Yongqiang , Zhang Donghang , Zhao Yijia (Eddie)
Published: September 2018

Using within-loan estimations to remove the impact of demand-side factors, we find that the capital levels of banks participating in the same syndicated loan are positively associated with the banks’ contributions to the loan. Consistent with the argument that higher capital reduces the cost of uninsured debt, the positive effect of bank capital on lending is stronger among banks that rely more on wholesale funding. Furthermore, we find that banks increase their contributions to syndicated loans after receiving Troubled Asset Relief Program (TARP) funding. Taken together, we provide new evidence on the importance and causal effect of bank capital on lending.
The illegal pet trade is driving Madagascar's ploughshare tortoise to extinction
Authors: Mandimbihasina Angelo R. , Woolaver Lance G. , Concannon Lianne E. , Milner-Gulland E. J. , Lewis Richard E. , Terry Andrew M.R. , Filazaha Niaraha , Rabetafika Lydia L. , Young Richard P.
Published: September 2018

The illegal wildlife trade is driving declines in populations of a number of large, charismatic animal species but also many lesser known and restricted-range species, some of which are now facing extinction as a result. The ploughshare tortoiseAstrochelys yniphora, endemic to the Baly Bay National Park of north-western Madagascar, is affected by poaching for the international illegal pet trade. To quantify this, we estimated population trends during 2006–2015, using distance sampling surveys along line transects, and recorded national and international confiscations of trafficked tortoises for 2002–2016. The results suggest the ploughshare tortoise population declined > 50% during this period, to c. 500 adults and subadults in 2014–2015. Prior to 2006 very few tortoises were seized either in Madagascar or internationally but confiscations increased sharply from 2010. Since 2015 poaching has intensified, with field reports suggesting that two of the four subpopulations are extinct, leaving an unknown but almost certainly perilously low number of adult tortoises in the wild. This study has produced the first reliable population estimate of the ploughshare tortoise and shows that the species has declined rapidly because of poaching for the international pet trade. There is an urgent need for increased action both in Madagascar and along international trade routes if the extinction of the ploughshare tortoise in the wild is to be prevented.
Peroxisome proliferator-activated receptor gamma co-activator-1 alpha in depression and the response to electroconvulsive therapy
Authors: Ryan Karen M. , Patterson Ian , McLoughlin Declan M.
Published: September 2018

Background

The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC-1α), termed the ‘master regulator of mitochondrial biogenesis’, has been implicated in stress and resilience to stress-induced depressive-like behaviours in animal models. However, there has been no study conducted to date to examine PGC-1α levels in patients with depression or in response to antidepressant treatment. Our aim was to assess PGC-1α mRNA levels in blood from healthy controls and patients with depression pre-/post-electroconvulsive therapy (ECT), and to examine the relationship between blood PGC-1α mRNA levels and clinical symptoms and outcomes with ECT.

Methods

Whole blood PGC-1α mRNA levels were analysed in samples from 67 patients with a major depressive episode and 70 healthy controls, and in patient samples following a course of ECT using quantitative real-time polymerase chain reaction (qRT-PCR). Exploratory subgroup correlational analyses were carried out to determine the relationship between PGC-1α and mood scores.

Results

PGC-1α levels were lower in patients with depression compared with healthy controls (p = 0.03). This lower level was predominantly accounted for by patients with psychotic unipolar depression (p = 0.004). ECT did not alter PGC-1α levels in the depressed group as a whole, though exploratory analyses revealed a significant increase in PGC-1α in patients with psychotic unipolar depression post-ECT (p = 0.045). We found no relationship between PGC-1α mRNA levels and depression severity or the clinical response to ECT.

Conclusions

PGC-1α may represent a novel therapeutic target for the treatment of depression, and be a common link between various pathophysiological processes implicated in depression.
X-ray powder diffraction data for 7-ethyl-14-nitro-camptothecin, C22H19N3O6
Authors: Wang Wan , Suo Zili , Liao Lidong , Li Hui
Published: September 2018

X-ray powder diffraction (XRD) data, unit-cell parameters and space group for 7-ethyl-14-nitro-camptothecin, C22H19N3O6, are reported [a = 10.987(5) Å, b = 10.941 (9) Å, c = 8.438 (2) Å, α = 71.321(6)°, β = 96.145(0)°, γ = 95.139(3)°, unit-cell volume V = 953.87 Å3, Z = 2, ρcal = 1.467 g cm−3, and space group P-1]. All measured lines were indexed and are consistent with the P-1 space group. No detectable impurities were observed.
Subjective social status and neural processing of race in Mexican American adolescents
Authors: Muscatell Keely A. , McCormick Ethan , Telzer Eva H.
Published: September 2018

Adolescence is a sensitive period for sociocultural development in which facets of social identity, including social status and race, become especially salient. Despite the heightened importance of both social status and race during this developmental period, no known work has examined how individual differences in social status influence perceptions of race in adolescents. Thus, in the present study, we investigated how both subjective social status and objective socioeconomic status (SES) influence neural responses to race. Twenty-three Mexican American adolescents (15 females; mean age = 17.22 years) were scanned using functional magnetic resonance imaging while they viewed Black and White faces in a standard labeling task. Adolescents rated their subjective social status in US society, while their parents responded to questions about their educational background, occupation, and economic strain (objective SES). Results demonstrated a negative association between subjective social status and neural responses in the amygdala, fusiform face area, and medial prefrontal cortex when adolescents viewed Black (relative to White) faces. In other words, adolescents with lower subjective social status showed greater activity in neural regions involved in processing salience, perceptual expertise, and thinking about the minds of others when they viewed images of Black faces, suggesting enhanced salience of race for these youth. There was no relationship between objective SES and neural responses to the faces. Moreover, instructing participants to focus on the gender or emotion expression on the face attenuated the relationship between subjective social status and neural processing of race. Together, these results demonstrate that subjective social status shapes the way the brain responds to race, which may have implications for psychopathology.
Arboreal birds do not avoid scattered trees in West Africa
Authors: ZWARTS LEO , BIJLSMA ROB G. , VAN DER KAMP JAN
Published: September 2018

Arboreal birds tend to remain in woody vegetation and avoid crossing open areas. Therefore, few tree-dwelling birds are to be expected in scattered trees. We tested this expectation with field data collected in the deserts, savannas and open agricultural parklands of West Africa where woody cover in 1,327 stratified random study sites varied between 0.2 and 29%. We found no evidence that scattered trees were avoided. Instead, bird density in trees was independent of trees occurring clumped or singly. The presence of birds in an individual tree was related to tree species and tree-related variables, but not to woody cover or species composition of the surrounding woody vegetation. We hypothesise that scattered trees are not avoided because (1) travel time between trees is too short to have a negative impact on foraging time, (2) predation risk of arboreal passerines is very low (bird-hunting raptors are scarce in the deserts and savannas of West Africa and mostly prey on ground-feeding, not arboreal, birds), and (3) the probability of being chased away by other arboreal birds is less when trees are more scattered. Scattered trees are ecologically important since hundreds of millions of migratory woodland birds, of which several species are in decline, spend the northern winter in Africa in open, often human-modified, landscapes where trees are well spaced.
Addenbrooke’s Cognitive Examination III: Psychometric Characteristics and Relations to Functional Ability in Dementia
Authors: So Matthew , Foxe David , Kumfor Fiona , Murray Cynthia , Hsieh Sharpley , Savage Greg , Ahmed Rebekah M. , Burrell James R. , Hodges John R. , Irish Muireann , Piguet Olivier
Published: September 2018

Objectives:The Addenbrooke’s Cognitive Examination (ACE) is a common cognitive screening test for dementia. Here, we examined the relationship between the most recent version (ACE-III) and its predecessor (ACE-R), determined ACE-III cutoff scores for the detection of dementia, and explored its relationship with functional ability.Methods:Study 1 included 199 dementia patients and 52 healthy controls who completed the ACE-III and ACE-R. ACE-III total and domain scores were regressed on their corresponding ACE-R values to obtain conversion formulae. Study 2 included 331 mixed dementia patients and 87 controls to establish the optimal ACE-III cutoff scores for the detection of dementia using receiver operator curve analysis. Study 3 included 194 dementia patients and their carers to investigate the relationship between ACE-III total score and functional ability.Results:Study 1: ACE-III and ACE-R scores differed by ≤1 point overall, the magnitude varying according to dementia type. Study 2: a new lower bound cutoff ACE-III score of 84/100 to detect dementia was identified (compared with 82 for the ACE-R). The upper bound cutoff score of 88/100 was retained. Study 3: ACE-III scores were significantly related to functional ability on the Clinical Dementia Rating Scale across all dementia syndromes, except for semantic dementia.Conclusions:This study represents one of the largest and most clinically diverse investigations of the ACE-III. Our results demonstrate that the ACE-III is an acceptable alternative to the ACE-R. In addition, ACE-III performance has broader clinical implications in that it relates to carer reports of functional impairment in most common dementias. (JINS, 2018,24, 854–863)
Submarine Groundwater Discharge‐Derived Carbon Fluxes in Mangroves: An Important Component of Blue Carbon Budgets?
Authors: Chen Xiaogang , Zhang Fenfen , Lao Yanling , Wang Xilong , Du Jinzhou , Santos Isaac R.
Published: September 2018

Mangroves are blue carbon systems characterized by high soil carbon storage and sequestration. Soil carbon losses via groundwater or pore water pathways are potentially important yet poorly understood components of mangrove carbon budgets. Here we quantified submarine groundwater discharge (SGD) and associated dissolved inorganic carbon (DIC) and organic carbon (DOC) fluxes into a mangrove‐dominated tropical bay (Maowei Sea) using a radon (222Rn) mass balance model. The SGD fluxes in Maowei Sea were estimated to be 4.9 × 107 (0.36 ± 0.33 m/day) and 2.6 × 107 m3/day (0.20 ± 0.18 m/day) for the wet and dry seasons, respectively, implying that SGD may respond to precipitation. The SGD‐derived DIC and DOC fluxes (mol·m−2·day−1) in the wet season (DIC: 0.70 ± 0.82; DOC: 0.31 ± 0.30) were higher than those in the dry season (DIC: 0.25 ± 0.24; DOC: 0.25 ± 0.23). These SGD‐derived carbon fluxes exceed local river inputs and constituted >70% of the total DIC and DOC input into the bay. If scaled up to the global weighted mangrove area in combination with data from other 32 study sites, carbon fluxes via SGD into mangroves may be equivalent to 29–48% of the global riverine input into the ocean. Therefore, we suggest that SGD is a major component of coastal carbon budgets and that accounting for SGD helps to reduce uncertainties in mangrove blue carbon budgets.
Size‐Resolved Dry Deposition Velocities of Dust Particles: In Situ Measurements and Parameterizations Testing
Authors: Bergametti G. , Marticorena B. , Rajot J. L. , Foret G. , Alfaro S. C. , Laurent B.
Published: September 2018

Bulk and size‐resolved particle concentrations were measured at 2.1 and 6.5 m above the soil surface during an intense dust deposition event that occurred in June 2006 in Niger. Bulk concentration measurements were performed using two tapered element oscillating microbalance instruments, and the size‐resolved particle concentrations (from 0.3 to 20 μm) using two optical particle counters. The deposition fluxes derived from the bulk concentrations and those derived from the size‐resolved ones are in very good agreement. The largest deposition fluxes are recorded when the dust concentrations are maximal. The temporal evolution of the dust deposition flux follows that of the dust concentration. This is not the case of the dry deposition velocities that are most of the time controlled by the wind friction velocity. The results also show that large particles are strongly sensible to rebound when the wind friction velocity is the highest. Size‐resolved dry deposition velocities are compared with the rare measurements of dust deposition velocities over bare sandy soils and are confronted to existing parameterizations of the dry deposition velocity. The parameterization of Zhang and Shao (2014, https://doi.org/10.5194/acp‐14‐12429‐2014) appears to be the only one able to reproduce satisfyingly the measured dry deposition velocities on sandy soils in the 1‐ to 10‐μm particle size range. Indeed, unlike others, this scheme considers the desert sandy surfaces as rough surfaces, allowing the interception of dust particles by the sand grains and/or by the small roughness elements present on the surface.
Development of an antibody fragment that stabilizes GPCR/G-protein complexes
Authors: Maeda Shoji , Koehl Antoine , Matile Hugues , Hu Hongli , Hilger Daniel , Schertler Gebhard F. X. , Manglik Aashish , Skiniotis Georgios , Dawson Roger J. P. , Kobilka Brian K.
Published: September 2018

Single-particle cryo-electron microscopy (cryo-EM) has recently enabled high-resolution structure determination of numerous biological macromolecular complexes. Despite this progress, the application of high-resolution cryo-EM to G protein coupled receptors (GPCRs) in complex with heterotrimeric G proteins remains challenging, owning to both the relative small size and the limited stability of these assemblies. Here we describe the development of antibody fragments that bind and stabilize GPCR-G protein complexes for the application of high-resolution cryo-EM. One antibody in particular, mAb16, stabilizes GPCR/G-protein complexes by recognizing an interface between Gα and Gβγ subunits in the heterotrimer, and confers resistance to GTPγS-triggered dissociation. The unique recognition mode of this antibody makes it possible to transfer its binding and stabilizing effect to other G-protein subtypes through minimal protein engineering. This antibody fragment is thus a broadly applicable tool for structural studies of GPCR/G-protein complexes.
NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease
Authors: Tye Hazel , Yu Chien-Hsiung , Simms Lisa A. , de Zoete Marcel R. , Kim Man Lyang , Zakrzewski Martha , Penington Jocelyn S. , Harapas Cassandra R. , Souza-Fonseca-Guimaraes Fernando , Wockner Leesa F. , Preaudet Adele , Mielke Lisa A. , Wilcox Stephen A. , Ogura Yasunori , Corr Sinead C. , Kanojia Komal , Kouremenos Konstantinos A. , De Souza David P. , McConville Malcolm J. , Flavell Richard A. , Gerlic Motti , Kile Benjamin T. , Papenfuss Anthony T. , Putoczki Tracy L. , Radford-Smith Graham L. , Masters Seth L.
Published: September 2018

Anti-microbial signaling pathways are normally triggered by innate immune receptors when detecting pathogenic microbes to provide protective immunity. Here we show that the inflammasome sensor Nlrp1 aggravates DSS-induced experimental mouse colitis by limiting beneficial, butyrate-producingClostridialesin the gut. The colitis-protective effects ofNlrp1deficiency are thus reversed by vancomycin treatment, but recapitulated with butyrate supplementation in wild-type mice. Moreover, an activating mutation inNlrp1aincreases IL-18 and IFNγ production, and decreases colonic butyrate to exacerbate colitis. We also show that, in patients with ulcerative colitis, increasedNLRP1in inflamed regions of the colon is associated with increasedIFN-γ. In this context,NLRP1,IL-18orIFN-γexpression negatively correlates with the abundance ofClostridialesin human rectal mucosal biopsies. Our data identify the NLRP1 inflammasome to be a key negative regulator of protective, butyrate-producing commensals, which therefore promotes inflammatory bowel disease.
The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory
Authors: Lee Boyoung , Bang Eunyoung , Yang Won Suk , Paydar Afshin , Ha Go Eun , Kim Sujin , Kim Jong-Hyun , Cho Taesup , Lee Seung Eun , Lee Sukchan , Kang Myoung-Goo , Cheong Eunji , Kim Key-Sun , Lee Cheolju , Yu Myeong-Hee , Shin Hee-Sup
Published: September 2018

Established fear memory becomes vulnerable to disruption after memory retrieval and extinction; this labile state is critical for inhibiting the return of fear memory. However, the labile state has a very narrow time window after retrieval, and underlying molecular mechanisms are not well known. To that end, we isolated the hippocampus immediately after fear memory retrieval and performed proteomics. We identified Neurobeachin (NBEA), an autism-related regulator of synaptic protein trafficking, to be upregulated after contextual fear memory retrieval. NBEA protein expression was rapid and transient after fear memory retrieval at the synapse. Nbea mRNA was enriched at the synapses, and the rapid induction of NBEA expression was blocked by inhibition of the mammalian target of rapamycin (mTOR)-dependent signaling pathway. Mice with cornu ammonis 1 (CA1)-specific Nbea shRNA knockdown showed normal fear acquisition and contextual fear memory but impaired extinction, suggesting an important role of Nbea in fear memory extinction processes. Consistently, Nbea heterozygotes showed normal fear acquisition and fear memory recall but showed impairment in extinction. Our data suggest that NBEA is necessary either for induction of memory lability or for the physiological process of memory extinction.
Recovery of horse fly populations in Louisiana marshes following the Deepwater Horizon oil spill
Authors: Husseneder Claudia , Park Jong-Seok , Foil Lane D.
Published: September 2018

The Deepwater Horizon oil spill in April 2010 had unprecedented impact on the Gulf of Mexico. We established the greenhead horse fly (Tabanus nigrovittatus Macquart) as a bioindicator of marsh health. This species is bound to coastal marshes, since its larvae develop as top invertebrate predators in the marsh soil. Immediately after the oil spill (2010–2011), populations of this horse fly declined in oiled areas of Louisiana marshes with significant impacts on genetic structure. In this follow-up study five years after the catastrophic event (2015–2016), we now report signs of recovery of populations in formerly oiled areas. Fly numbers increased compared to previous counts. Previously detected genetic bottlenecks in oiled populations have disappeared. Migration into oiled areas began to replenish formerly depleted horse fly populations in impacted regions with populations from non-oiled areas as an important source of migrants. Parameters of family structure that had been impacted by the oil spill (number of breeding parents, effective population size, number of family clusters) rebounded to levels similar to or exceeding those in non-oiled control areas.
Link between carrot leaf secondary metabolites and resistance to Alternaria dauci
Authors: Koutouan Claude , Clerc Valérie Le , Baltenweck Raymonde , Claudel Patricia , Halter David , Hugueney Philippe , Hamama Latifa , Suel Anita , Huet Sébastien , Merlet Marie-Hélène Bouvet , Briard Mathilde
Published: September 2018

Alternaria Leaf Blight (ALB), caused by the fungus Alternaria dauci, is the most damaging foliar disease affecting carrots (Daucus carota). In order to identify compounds potentially linked to the resistance to A. dauci, we have used a combination of targeted and non-targeted metabolomics to compare the leaf metabolome of four carrot genotypes with different resistance levels. Targeted analyses were focused on terpene volatiles, while total leaf methanolic extracts were subjected to non-targeted analyses using liquid chromatography couple to high-resolution mass spectrometry. Differences in the accumulation of major metabolites were highlighted among genotypes and some of these metabolites were identified as potentially involved in resistance or susceptibility. A bulk segregant analysis on F3 progenies obtained from a cross between one of the resistant genotypes and a susceptible one, confirmed or refuted the hypothesis that the metabolites differentially accumulated by these two parents could be linked to resistance.
Missense mutation of VKORC1 leads to medial arterial calcification in rats
Authors: Michaux Arnaud , Matagrin Benjamin , Debaux Jean-Valéry , Schurgers Leon J. , Benoit Etienne , Lattard Virginie
Published: September 2018

Vitamin K plays a crucial role in the regulation of vascular calcifications by allowing activation of matrix Gla protein. The dietary requirement for vitamin K is low because of an efficient recycling of vitamin K by vitamin K epoxide reductase (VKORC1). However, decreased VKORC1 activity may result in vascular calcification. More than 30 coding mutations of VKORC1 have been described. While these mutations have been suspected of causing anticoagulant resistance, their association with an increase in the risk of vascular calcification has never been considered. We thus investigated functional cardiovascular characteristics in a rat model mutated in VKORC1. This study revealed that limited intake in vitamin K in mutated rat induced massive calcified areas in the media of arteries of lung, aortic arch, kidneys and testis. Development of calcifications could be inhibited by vitamin K supplementation. In calcified areas, inactive Matrix Gla protein expression increased, while corresponding mRNA expression was not modified. Mutation in VKORC1 associated with a limited vitamin K intake is thus a major risk for cardiovascular disease. Our model is the first non-invasive rat model that shows spontaneous medial calcifications and would be useful for studying physiological function of vitamin K.
Copper mediated amyloid-β binding to Transthyretin
Authors: Ciccone Lidia , Fruchart-Gaillard Carole , Mourier Gilles , Savko Martin , Nencetti Susanna , Orlandini Elisabetta , Servent Denis , Stura Enrico A. , Shepard William
Published: September 2018

Transthyretin (TTR), a homotetrameric protein that transports thyroxine and retinol both in plasma and in cerebrospinal (CSF) fluid provides a natural protective response against Alzheimer’s disease (AD), modulates amyloid-β (Aβ) deposition by direct interaction and co-localizes with Aβ in plaques. TTR levels are lower in the CSF of AD patients. Zn2+, Mn2+ and Fe2+ transform TTR into a protease able to cleave Aβ. To explain these activities, monomer dissociation or conformational changes have been suggested. Here, we report that when TTR crystals are exposed to copper or iron salts, the tetramer undergoes a significant conformational change that alters the dimer-dimer interface and rearranges residues implicated in TTR’s ability to neutralize Aβ. We also describe the conformational changes in TTR upon the binding of the various metal ions. Furthermore, using bio-layer interferometry (BLI) with immobilized Aβ(1–28), we observe the binding of TTR only in the presence of copper. Such Cu2+-dependent binding suggests a recognition mechanism whereby Cu2+ modulates both the TTR conformation, induces a complementary Aβ structure and may participate in the interaction. Cu2+-soaked TTR crystals show a conformation different from that induced by Fe2+, and intriguingly, TTR crystals grown in presence of Aβ(1–28) show different positions for the copper sites from those grown its absence.
Global establishment threat from a major forest pest via international shipping: Lymantria dispar
Authors: Paini D. R. , Mwebaze P. , Kuhnert P. M. , Kriticos D. J.
Published: September 2018

The global shipping network is widely recognised as a pathway for vectoring invasive species. One species of particular concern is Lymantria dispar (gypsy moth). Two subspecies, L. d. asiatica and L. d. japonica (herein referred to as Asian Gypsy Moth - AGM) are of considerable concern as ships arriving to a number of countries have been found carrying AGM egg masses. However, ships carrying AGM eggs can only threaten a country at ports located in a climatically suitable region. We present a CLIMEX model of climate suitability and combine this with international shipping to estimate the global threat from AGM. We find that for the USA more than half of international ships (approximately 18,000 ships) arrive to climatically suitable ports. Other countries with a large number of ships arriving to ports with suitable climates include Canada and Brazil. This is the first global analysis of the invasion threat from AGM, and we recommend countries focus AGM-inspection programs towards ships arriving at ports found within climatically suitable regions.
Highly transparent light emitting diodes on graphene encapsulated Cu nanowires network
Authors: Huang Youyang , Huang Zongxing , Zhong Zhibai , Yang Xu , Hong Qiming , Wang Huachun , Huang Shengrong , Gao Na , Chen Xiaohong , Cai Duanjun , Kang Junyong
Published: September 2018

The internal quantum efficiency of blue LEDs is almost close to the limit, therefore, advanced transparent electrode has been long explored for gaining high external quantum efficiency. However, work function mismatch at electrode-semiconductor interface remains the fundamental difficulty in obtaining low resistance ohmic contact. Here, we demonstrate the gas phase encapsulation of graphene layer on superfine Cu nanowires network by chemical vapor deposition for highly transparent LEDs. The fast encapsulation of graphene shell layer on Cu nanowires achieves high optoelectronic performance (33 Ω/sq @ 95% T), broad transparency range (200~3000 nm) and strong antioxidant stability. A novel phenomenon of scattered-point contact is revealed at the Cu nanowires/GaN interface. Point discharge effect is found to produce locally high injection current through contact points, which can effectively overcome Schottky barrier and form ohmic contact. The transparent LED on Cu@graphene nanowire network is successfully lighted with bright blue emission.
Artificial Shape Perception Retina Network Based on Tunable Memristive Neurons
Authors: Bao Lin , Kang Jian , Fang Yichen , Yu Zhizhen , Wang Zongwei , Yang Yuchao , Cai Yimao , Huang Ru
Published: September 2018

Retina shows an extremely high signal processing efficiency because of its specific signal processing strategy which called computing in sensor. In retina, photoreceptor cells encode light signals into spikes and ganglion cells finish the shape perception process. In order to realize the neuromorphic vision sensor, the one-transistor-one-memristor (1T1M) structure which formed by one memristor and one MOSFET in serial is used to construct photoreceptor cell and ganglion cell. The voltage changes between two terminals of memristor and MOSFET can mimic the changes of membrane potential caused by spikes and illumination respectively. In this paper, the tunable memristive neurons with 1T1M structures are built. According to the concept of receptive field of ganglion cells (GCs) in the retina, the artificial shape perception retina network is constructed with these memristive neurons. The final results show that the artificial retina can extract shape information from the image and transfer it into spike frequency realizing the function of computing in sensor.
Volume phase transition kinetics of smart N-n-propylacrylamide microgels studied by time-resolved pressure jump small angle neutron scattering
Authors: Wrede Oliver , Reimann Yvonne , Lülsdorf Stefan , Emmrich Daniel , Schneider Kristina , Schmid Andreas Josef , Zauser Diana , Hannappel Yvonne , Beyer André , Schweins Ralf , Gölzhäuser Armin , Hellweg Thomas , Sottmann Thomas
Published: September 2018

The use of smart colloidal microgels for advanced applications critically depends on their response kinetics. We use pressure jump small angle neutron scattering with supreme time resolution to study the rapid volume phase transition kinetics of such microgels. Utilizing the pressure induced microphase separation inside the microgels we were able to resolve their collapse and swelling kinetics. While the collapse occurs on a time scale of 10 ms, the particle swelling turned out to be much faster. Photon correlation spectroscopy and static small angle neutron scattering unambiguously show, that the much slower collapse can be associated with the complex particle architecture exhibiting a loosely-crosslinked outer region and a denser inner core region. These insights into the kinetics of stimuli-responsive materials are of high relevance for their applications as nano-actuators, sensors or drug carriers. Moreover, the used refined pressure jump small angle neutron scattering technique is of broad interest for soft matter studies.
Behavioral performance and visual strategies during skill acquisition using a novel tool use motor learning task
Authors: Bosch T. J. , Hanna T. , Fercho K. A. , Baugh L. A.
Published: September 2018

Habitual tool use is considered a hallmark of human evolution. One potential explanation for humanity’s advanced tool using abilities is that humans possess a unique neurobiological system that estimates efficient ways to manipulate objects with novel tools, resulting in rapid tool use motor learning. However, since humans regularly use a multitude of tools, examining these underlying processes is challenging. As such, we developed a tool use motor learning paradigm that utilizes a challenging tool (chopsticks) in order to accomplish a difficult behavioral task that requires extensive practice to continuously improve one’s proficiency. We then assessed the paradigm by recruiting participants with little experience using chopsticks and training them over the course of eight training sessions to grasp marbles with chopsticks and drop them in a cylindrical container. Throughout training, we examined behavioral performance and visual strategies to determine whether practicing the task resulted in outcomes congruent with traditional motor learning. Results show that performance increases in a logarithmic pattern and is accompanied by decreased confirmatory visual strategies. Since these findings are congruent with those seen in traditional motor learning, this paradigm is a novel method for use in future research examining the underlying mechanisms that mediate tool use motor learning.
Optogenetic stimulation of complex spatio-temporal activity patterns by acousto-optic light steering probes cerebellar granular layer integrative properties
Authors: Hernandez Oscar , Pietrajtis Katarzyna , Mathieu Benjamin , Dieudonné Stéphane
Published: September 2018

Optogenetics provides tools to control afferent activity in brain microcircuits. However, this requires optical methods that can evoke asynchronous and coordinated activity within neuronal ensembles in a spatio-temporally precise way. Here we describe a light patterning method, which combines MHz acousto-optic beam steering and adjustable low numerical aperture Gaussian beams, to achieve fast 2D targeting in scattering tissue. Using mossy fiber afferents to the cerebellar cortex as a testbed, we demonstrate single fiber optogenetic stimulation with micron-scale lateral resolution, >100 µm depth-penetration and 0.1 ms spiking precision. Protracted spatio-temporal patterns of light delivered by our illumination system evoked sustained asynchronous mossy fiber activity with excellent repeatability. Combining optical and electrical stimulations, we show that the cerebellar granular layer performs nonlinear integration, whereby sustained mossy fiber activity provides a permissive context for the transmission of salient inputs, enriching combinatorial views on mossy fiber pattern separation.
Blocking HIF signaling via novel inhibitors of CA9 and APE1/Ref-1 dramatically affects pancreatic cancer cell survival
Authors: Logsdon Derek P. , Shah Fenil , Carta Fabrizio , Supuran Claudiu T. , Kamocka Malgorzata , Jacobsen Max H. , Sandusky George E. , Kelley Mark R. , Fishel Melissa L.
Published: September 2018

Pancreatic ductal adenocarcinoma (PDAC) has reactive stroma that promotes tumor signaling, fibrosis, inflammation, and hypoxia, which activates HIF-1α to increase tumor cell metastasis and therapeutic resistance. Carbonic anhydrase IX (CA9) stabilizes intracellular pH following induction by HIF-1α. Redox effector factor-1 (APE1/Ref-1) is a multifunctional protein with redox signaling activity that converts certain oxidized transcription factors to a reduced state, enabling them to upregulate tumor-promoting genes. Our studies evaluate PDAC hypoxia responses and APE1/Ref-1 redox signaling contributions to HIF-1α-mediated CA9 transcription. Our previous studies implicated this pathway in PDAC cell survival under hypoxia. We expand those studies, comparing drug responses using patient-derived PDAC cells displaying differential hypoxic responses in 3D spheroid tumor-stroma models to characterize second generation APE1/Ref-1 redox signaling and CA9 inhibitors. Our data demonstrates that HIF-1α-mediated CA9 induction differs between patient-derived PDAC cells and that APE1/Ref-1 redox inhibition attenuates this induction by decreasing hypoxia-induced HIF-1 DNA binding. Dual-targeting of APE1/Ref-1 and CA9 in 3D spheroids demonstrated that this combination effectively kills PDAC tumor cells displaying drastically different levels of CA9. New APE1/Ref-1 and CA9 inhibitors were significantly more potent alone and in combination, highlighting the potential of combination therapy targeting the APE1-Ref-1 signaling axis with significant clinical potential.
Earth’s Subdecadal Angular Momentum Balance from Deformation and Rotation Data
Authors: Watkins Andrew , Fu Yuning , Gross Richard
Published: September 2018

Length-of-Day (LOD) measurements represent variations in the angular momentum of the solid Earth (crust and mantle). There is a known ~6-year LOD signal suspected to be due to core-mantle coupling. If it is, then the core flow associated with the 6-year LOD signal may also deform the mantle, causing a 6-year signal in the deformation of the Earth’s surface. Stacking of Global Positioning System (GPS) data is found to contain a ~6-year radial deformation signal. We inverted the deformation signal for the outer core’s flow and equivalent angular momentum changes, finding good agreement with the LOD signal in some cases. These results support the idea of subdecadal core-mantle coupling, but are not robust. Interpretation of the results must also take into account methodological limitations. Gravitational field changes resulting from solid Earth deformation were also computed and found to be smaller than the errors in the currently available data.
Exploration of ligand binding modes towards the identification of compounds targeting HuR: a combined STD-NMR and Molecular Modelling approach
Authors: Vasile Francesca , Della Volpe Serena , Ambrosio Francesca Alessandra , Costa Giosuè , Unver M. Yagiz , Zucal Chiara , Rossi Daniela , Martino Emanuela , Provenzani Alessandro , Hirsch Anna K. H. , Alcaro Stefano , Potenza Donatella , Collina Simona
Published: September 2018

Post-transcriptional processes have been recognised as pivotal in the control of gene expression, and impairments in RNA processing are reported in several pathologies (i.e., cancer and neurodegeneration). Focusing on RNA-binding proteins (RBPs), the involvement of Embryonic Lethal Abnormal Vision (ELAV) or Hu proteins and their complexes with target mRNAs in the aetiology of various dysfunctions, has suggested the great potential of compounds able to interfere with the complex stability as an innovative pharmacological strategy for the treatment of numerous diseases. Here, we present a rational follow-up investigation of the interaction between ELAV isoform HuR and structurally-related compounds (i.e., flavonoids and coumarins), naturally decorated with different functional groups, by means of STD-NMR and Molecular Modelling. Our results represent the foundation for the development of potent and selective ligands able to interfere with ELAV–RNA complexes.
Tracking Fish Abundance by Underwater Image Recognition
Authors: Marini Simone , Fanelli Emanuela , Sbragaglia Valerio , Azzurro Ernesto , Del Rio Fernandez Joaquin , Aguzzi Jacopo
Published: September 2018

Marine cabled video-observatories allow the non-destructive sampling of species at frequencies and durations that have never been attained before. Nevertheless, the lack of appropriate methods to automatically process video imagery limits this technology for the purposes of ecosystem monitoring. Automation is a prerequisite to deal with the huge quantities of video footage captured by cameras, which can then transform these devices into true autonomous sensors. In this study, we have developed a novel methodology that is based on genetic programming for content-based image analysis. Our aim was to capture the temporal dynamics of fish abundance. We processed more than 20,000 images that were acquired in a challenging real-world coastal scenario at the OBSEA-EMSO testing-site. The images were collected at 30-min. frequency, continuously for two years, over day and night. The highly variable environmental conditions allowed us to test the effectiveness of our approach under changing light radiation, water turbidity, background confusion, and bio-fouling growth on the camera housing. The automated recognition results were highly correlated with the manual counts and they were highly reliable when used to track fish variations at different hourly, daily, and monthly time scales. In addition, our methodology could be easily transferred to other cabled video-observatories.