bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrospinal fluid tau, Aβ, and sTREM2 in Former National Football League Players: Modeling the relationship between repetitive head impacts, microglial activation, and neurodegeneration
Authors: Alosco Michael L. , Tripodis Yorghos , Fritts Nathan G. , Heslegrave Amanda , Baugh Christine M. , Conneely Shannon , Mariani Megan , Martin Brett M. , Frank Samuel , Mez Jesse , Stein Thor D. , Cantu Robert C. , McKee Ann C. , Shaw Leslie M. , Trojanowski John Q. , Blennow Kaj , Zetterberg Henrik , Stern Robert A.
Published: July 2018

Introduction

Cerebrospinal fluid (CSF) protein analysis may facilitate detection and elucidate mechanisms of neurological consequences from repetitive head impacts (RHI), such as chronic traumatic encephalopathy. We examined CSF concentrations of total tau (t‐tau), phosphorylated tau, and amyloid β1‐42 and their association with RHI in former National Football League (NFL) players. The role of microglial activation (using sTREM2) was examined as a pathogenic mechanism of chronic traumatic encephalopathy.

Methods

Sixty‐eight former NFL players and 21 controls underwent lumbar puncture to quantify t‐tau, p‐tau181, amyloid β1‐42, and sTREM2 in the CSF using immunoassays. The cumulative head impact index estimated RHI.

Results

No between‐group differences for CSF analytes emerged. In the former NFL players, the cumulative head impact index predicted higher t‐tau concentrations (P = .041), and higher sTREM2 levels were associated with higher t‐tau concentrations (P = .009).

Discussion

In this sample of former NFL players, greater RHI and increased microglial activation were associated with higher CSF t‐tau concentrations.
Behavior in reverse: reasons for return migration
Authors: STARK ODED
Published: July 2018

Received research shows numerous motives for migration, but fewer reasons for return migration. This paper aims to correct this imbalance. Twelve reasons for return migration are presented and discussed briefly. The reasons listed are derived from research on migration conducted by the author in the course of the past three and a half decades. The purpose of the paper is to pull together insights gained from that research so as to formulate a base for future inquiry, both analytical and empirical. In addition, just as research on motives for migration can help to establish the reasons for return migration, research on the latter can help to deepen understanding of the former. Moreover, in a great many circumstances and for a variety of reasons, countries that host migrants may want them to leave. In such circumstances, enacting policies that align with motives for return migration will be more efficient than devising measures that are independent of these motives.
SINGULARITIES OF THE BIEXTENSION METRIC FOR FAMILIES OF ABELIAN VARIETIES
Authors: BURGOS GIL JOSÉ IGNACIO , HOLMES DAVID , JONG ROBIN DE
Published: July 2018

In this paper we study the singularities of the invariant metric of the Poincaré bundle over a family of abelian varieties and their duals over a base of arbitrary dimension. As an application of this study we prove the effectiveness of the height jump divisors for families of pointed abelian varieties. The effectiveness of the height jump divisor was conjectured by Hain in the more general case of variations of polarized Hodge structures of weight $-1$.
Altaethyrella(Brachiopoda) from the Late Ordovician of the Tarim Basin, Northwest China, and its significance
Authors: Sproat Colin D. , Zhan Renbin
Published: July 2018

Altaethyrella tarimensis, a new species of rhynchonellide brachiopod, is described from the late Katian (Late Ordovician) Hadabulaktag Formation in the Kuruktag region of Xinjiang, Northwest China on the northeastern edge of the Tarim Basin. Serial sections of the shell clearly show no dorsal median septum or septalium in the dorsal valve, and no spiralia or atrypide-style crura. Like other species of the genus,A.tarimensisn. sp. exhibits a high degree of intraspecific variation, including variations in shell shape and size, number of ribs in the sulcus at the anterior, and degree of asymmetry. The discovery ofAltaethyrellain Tarim has important paleogeographic implications, indicating a close relationship between the Late Ordovician brachiopod faunas of Tarim and those of the Kazakh terranes and North and South China paleoplates, supporting a recently published paleogeographic projection that places Tarim near the Chu-Ili terrane during the Late Ordovician. The abundant large biconvex shells ofA.tarimensisn. sp. would have provided a firm substrate for encrusting filter feeders like bryozoans to establish on the Kuruktag Platform.

UUID:http://zoobank.org/df8843cd-4db0-48e7-ba03-bf0ce81c4f01
A comparison of sexual competitiveness and demographic traits ofAnastrepha obliqua(Macquart) (Diptera: Tephritidae) among fruit-associated populations
Authors: Hernández E. , Ruiz-Montoya L. , Toledo J. , Montoya P. , Liedo P. , Aceituno-Medina M. , Perales H.
Published: July 2018

The control ofAnastrepha obliquaincludes the sterilization of mass-reared insects grown in isolation in a constantly controlled environment. Through time, laboratory mass-reared colonies may produce flies with lower field performance. To recover the genetic variation and aptitude of mass-reared populations, wild insects are introduced into mass-reared colonies. Our aim in this study was to determine whether the host species from two localities influence the life history traits ofA. obliqua. We collected flies as larvae from infested fruits ofSpondias purpurea,S. mombin,Mangifera indicacv.‘piña’, andM. indicacv. ‘coche’ from two localities in Chiapas, Mexico. There were significant differences in the mating competitiveness of males collected from mango cv. ‘coche’ compared with mass-reared males. There were no differences in the mating propensity between flies from the two localities, even in the number of matings, when weight was considered as a covariable. The mass-reared strain showed the earliest age at first oviposition. The locality affected the longevity and oviposition period, and these influenced the birth rate, intrinsic rate of increase, finite rate of population increase, mean generation time, and doubling time. According to the demographic parameters, the population ofS. mombinwould allow artificial colonization in less time, considering that it has a high reproduction rate starting at an early age. Even in the propensity test, it had the highest number of matings. However, males with greater sexual competitiveness and longevity for colonization corresponded to those collected fromS. purpurea.
The importance of petrous apex and peri-carotid pneumatisation in subtotal petrosectomy and blind sac closure: a radiological study
Authors: McKay-Davies I , Selvarajah K , Neeff M , Sillars H
Published: July 2018

Objective

To ascertain in what proportion the vertical segment of the intratemporal carotid artery on its medial aspect anatomically separates the peri-tubal cells and Eustachian tube from the remainder of the pneumatised spaces of the temporal bone.

Method

A retrospective review was conducted of 222 adult and 29 paediatric consecutive computed tomography scans of petrous temporal bones from a single tertiary referral centre.

Results

In 96 per cent of temporal bones, the carotid artery formed a lateral barrier (with no communication pathway medially) between air spaces anterior and posterior to it. This equated to 94 per cent when chronic otitis media cases were excluded.

Conclusion

The degree of separation of middle-ear air cells from the Eustachian tube or nasopharynx, and the relevant anatomy, are reviewed. This knowledge helps to optimise the outcome of subtotal petrosectomy and blind sac closure. The frequency and process of pneumatisation of the petrous apex, and its connections with the middle ear, have been radiologically confirmed.
Caloplaca sol(Teloschistaceae), a new coastal lichen from Great Britain
Authors: ORANGE Alan
Published: July 2018

Caloplaca solis described as a new species from limestone and basic siliceous rocks on the southern and western coasts of Great Britain. It is characterized by a well-developed, crustose, non-placodioid, epilithic, cracked, orange-yellow thallus, almost concolorous apothecia up to 0·66 mm diameter, and ascosporesc. 11·0–12·2–13·0 µm long with a septumc. 0·4×the ascospore length.Caloplaca dalmaticais related but differs in the endolithic or only thinly epilithic thallus.Caloplaca marinais darker orange in colour, with more convex areoles, and is mostly confined to the splash zone of the seashore.Caloplaca maritimadiffers in the typically more convex, sometimes isolated areoles, and often in the presence of a crenulate thalline margin in young apothecia.Caloplaca itianais newly reported from Great Britain from coastal limestone; it differs fromC. solin the thallus being endolithic or almost so, and fromC. dalmaticain the more completely endolithic thallus and the larger ascospores.
Fuscidea lightfootiiandF.pusilla(Fuscideaceae, Umbilicariomycetidae, Ascomycota), two similar but genetically distinct species.
Authors: ZAHRADNíKOVá Martina , ANDERSEN Heidi Lie , TøNSBERG Tor
Published: July 2018

The two corticolous speciesFuscidea lightfootii(Sm.) Coppins & P. James andF.pusillaTønsberg are morphologically and chemically similar and it has been suggested that they are conspecific. We investigated the interspecific relationship betweenF. lightfootiiandF.pusillausing ITS, LSU and mtSSU rDNA. The combined multigene phylogeny shows that these species are genetically distinct. They are similar in ascocarp anatomy but in thallus morphology and substratum preferences there may be slight differences between them. Moreover,F. pusilladisplays a broader ecological range thanF.lightfootii. Even though some morphotypes appeared distinct and may be assigned to one of the two species with some degree of certainty, the use of DNA sequencing is recommended for their identification. Epitypes are designated for both species.
Sporastatia crassulata, a new species from the Altai Mountains with a key toSporastatiaand remarks on some additional species
Authors: YAKOVCHENKO Lidia S. , DAVYDOV Evgeny A.
Published: July 2018

Sporastatia crassulataYakovchenko & Davydov sp. nov. is described and a phylogenetic analysis (mtSSU) is presented, confirming its distinctness and indicating a sister relationship withS.testudinea. The species is unique amongSporastatiaspecies in having a distinctly squamulose, thick, uneven thallus composed of convex, rounded squamules irregularly ascending in the central part of the thallus. The new combinationSporastatia karakorina(Poelt & Obermayer) Davydov & Yakovchenko is proposed. The type specimen ofS.subasiaticawas examined. A key to the six species ofSporastatiais given. Mountainous Central Asia appears to be the centre of species diversity and endemism forSporastatia.
The Silk Road and the Iranian political economy in late antiquity: Iran, the Silk Road, and the problem of aristocratic empire
Authors: Payne Richard E.
Published: July 2018

The Iranian Empire emerged in the third century in the interstices of the Silk Road that increasingly linked the markets of the Mediterranean and the Near East with South, Central, and East Asia. The ensuing four centuries of Iranian rule corresponded with the heyday of trans-Eurasian trade, as the demand of moneyed imperial elites across the continent for one another's high-value commodities stimulated the development of long-distance networks. Despite its position at the nexus of trans-continental and trans-oceanic commerce, accounts of Iran in late antiquity relegate trade to a marginal role in its political economy. The present article seeks to foreground the contribution of trans-continental mercantile networks to the formation of Iran and to argue that its development depended as much on the political economies of its western and eastern neighbours as on internal Near Eastern factors.
The origin of the Semitic relative marker
Authors: Huehnergard John , Pat-El Na‘ama
Published: July 2018

All Semitic languages use a relative marker as at least one strategy of relativization, and all branches show reflexes or relics of reflexes of an interdental relative marker. The wide consensus that the relative pronoun was originally identical to the proximal demonstrative is based on the formal identity between the bases of the two in West Semitic, and on the wide attestation of the process Demonstrative > Relative in world languages. In this paper, we will show that there are a number of significant problems with the reconstruction of the relative pronoun, which, when taken together, make tracing its origin to the demonstrative highly unlikely. Instead we will argue that the opposite is true: the demonstrative in West Semitic is a secondary formation on the basis of the relative marker.
Applebaum, Fitzpatrick and the Genocide Question
Authors: NAIMARK NORMAN M.
Published: July 2018

Both Sheila Fitzpatrick and Anne Applebaum are fine historians who have made important contributions to the historiography of the Soviet Union. Applebaum works as a journalist and writer. But that is no reason to sniff at her contributions as ‘popular history’ or ‘history light’. In the books I have read, Gulag: A History (2003), Iron Curtain (2012) and Red Famine (2017), she has always strived to document her assertions, present logical and well-honed arguments and use archival and other documentary material where possible to forge new paths. One might not always agree with her conclusions, but that is a different question. If only more of our colleagues could write as well as Applebaum, think as clearly and attack important subjects the way she does, we would have a richer historiography as a result.
Ukraine and Kazakhstan: Comparing the Famines
Authors: PIANCIOLA NICCOLÒ
Published: July 2018

Anne Applebaum is one of the most prominent public intellectuals and opinion makers battling the on-going authoritarian and populist drive on both sides of the Atlantic. Her public commitment to denouncing Putin's authoritarian regime and its aggression against Ukraine is closely related to the pages of Red Famine, which tackles the most contentious historical event dividing the Russian and Ukrainian political classes.
From a Local Erfahrungsgeschichte of Holodomor to a Global History of Famines
Authors: PENTER TANJA
Published: July 2018

In German historiography, the Ukrainian famine has not received adequate attention. A few exceptions exist, such as the 2004 special issue of the journal Osteuropa edited by Gerhard Simon and Rudolf Mark, but no single monograph in the German language nor any research project deals with the Holodomor. Moreover, amongst the broader German public, the Soviet famine of 1932–3 is relatively unknown, despite being one of the great catastrophes in twentieth-century European history and (in terms of its death toll) one of the biggest single crimes of Stalinism. How can this obvious omission on the part of German academic researchers of Stalinism be explained?
From Iron Curtain to Velvet Curtain? Peter Brook'sHamletand the Origins of British–Soviet Cultural Relations during the Cold War
Authors: DAVIES SARAH
Published: July 2018

The article assesses the significance of the Moscow tour of Peter Brook'sHamlet. It considers how far the tour succeeded in overcoming the symbolic iron curtain by examining whatHamletmeant for contemporaries on both sides of the political divide. It argues that theHamlettour served at once to perpetuate and undermine the divisions between East and West, confirming Iriye's observation that on one level the Cold War intensified antagonism between states, while on another it helped to foster the growth of internationalist sentiment.
Surgical management of CHD in the adult population: the role of humanitarian cardiac surgery mission in Nigeria
Authors: Nwafor Ikechukwu A. , Eze John C.
Published: July 2018

Background

The clinical effects of CHD can occur during the neonatal period, childhood, adolescent, and even adulthood. Some CHD in the adult population have indications for surgical management.

Objective

The objective of this study was to review the role of humanitarian cardiac surgery missions in the surgical management of CHD in the adult population in a developing country.

Materials and method

Over a 5.5-year period – June, 2003, February, 2013–October, 2017 – five different humanitarian cardiac surgery teams visited National Cardiothoracic Center of Excellence, Nigeria. During the period, they operated on adults with CHD. A retrospective study of the patients treated was performed using data obtained from our Hospital Information Technology Department. The demography of the patients, types of CHD, operative modalities, as well as the outcome was analysed using Microsoft Excel. The results were presented in arithmetic of percentages using tables.

Results

During the period, a total of 18 CHD patients were treated.
Overcoming the “Logic of Exception”: A Critique of the UN Security Council’s Response to Environmental Damage from the 1990–91 Gulf War
Authors: CUSATO Eliana
Published: July 2018

This paper examines the UN Security Council’s [UNSC] response to the environmental impact of the 1990–91 Gulf War and its relevance to ongoing debates on environmental protection during armed conflict. With Resolution 687/91, the UNSC referred to “environmental damage and depletion of natural resources” in the context of war reparations, and established the UN Compensation Commission [UNCC] to process environmental claims. Whilst this is often hailed as a success story, this paper raises questions about certain dimensions of the UNCC: the choice of the applicable law; the decision-making process, particularly in relation to causation and remedies; and its punitive/biased nature. It argues that the successful outcome of the environmental compensation regime cannot be separated from the UNCC’s exceptional application of international legal norms. By drawing attention to this “logic of exception”, I suggest that alternative responses, more attentive to the dynamics of contemporary conflicts and their multiple environmental impacts, should be imagined.
The Place of Nusantara in the Sanskritic Buddhist Cosmopolis
Authors: Acri Andrea
Published: July 2018

This article synthesizes and links together evidence published thus far in secondary literature, in order to highlight the contribution of Nusantara to the genesis and circulation of various forms of Sanskritic Buddhism across Asia from the fifth to the fourteenth century. It places particular emphasis on its expansion via maritime routes. Archaeological vestiges and textual sources suggest that Nusantara was not a periphery, but played a constitutive, Asia-wide role as both a crossroads and terminus of Buddhist contacts since the early centuries of the Common Era. Sumatra, Java, and the Malay Peninsula hosted major centres of Buddhist worship and higher learning that were fully integrated into the trans-Asian maritime network of trade, diplomacy, and pilgrimage. Frequented by some of the most eminent Buddhist personalities of their times, who prompted doctrinal and cultic developments in South and East Asia, Nusantara may have exerted an influence on paradigms of Sanskritic Buddhism across Asia, rather than being a passive recipient of ideas and practices.
A Meta-Analysis of Field Bindweed (Convolvulus arvensis) Management in Annual and Perennial Systems
Authors: Davis Stacy , Mangold Jane , Menalled Fabian , Orloff Noelle , Miller Zach , Lehnhoff Erik
Published: July 2018

Field bindweed (Convolvulus arvensisL.) is a persistent, perennial weed species that infests a variety of temperate habitats around the globe. To evaluate the efficacy of general management approaches and impacts on crop yield and to identify research gaps, we conducted a series of meta-analyses using published studies focusing onC. arvensismanagement in annual cropping and perennial systems. Our analysis of 48 articles (560 data points) conducted in annual systems indicated that 95% of data points measured efficacy over short time frames (within 2 yr of treatment). Furthermore, only 27% of data points reported impacts ofC. arvensismanagement on crop yield. In annual systems, herbicide control dominated the literature (~80% of data points) and was an effective management technique up to 2 yr posttreatment. Integrated management, with or without herbicides, and three nonchemical techniques were similarly effective as herbicide at reducingC. arvensisup to 2 yr posttreatment. In addition, integrated approaches, with or without herbicides, and two nonchemical techniques had positive effects on crop yield. There were few differences among herbicide mechanism of action groups onC. arvensisabundance in annual systems. There were only nine articles (28 data points) concerningC. arvensismanagement in perennial systems (e.g., pasture, rangeland, lawn), indicating more research effort has been directed toward annual systems. In perennial systems, biocontrol, herbicide, and non-herbicide integrated management techniques were equally effective at reducingC. arvensis, while competition and grazing were not effective. Overall, our results demonstrate that while chemical control ofC. arvensisis generally effective and well studied, integrated and nonchemical control practices can perform equally well. We also documented the need for improved monitoring of the efficacy of management practices over longer time frames and including effects on desired vegetation to develop sustainable weed management programs.
Growth, Fitness, and Overwinter Survival of a Shattercane (Sorghum bicolorssp.drummondii)×Grain Sorghum (Sorghum bicolorssp.bicolor) F2Population
Authors: Schmidt Jared J. , Yerka Melinda K. , Pedersen Jeffrey F. , Lindquist John L.
Published: July 2018

Although sorghum [Sorghum bicolor(L.) Moench ssp.bicolor] is the fifth most important grain crop in terms of global production, no commercial hybrids carry genetically engineered (GE) traits for resistance to insect pests or herbicides due to regulatory concerns about gene flow to weedy relatives. However, non-GE herbicide resistance currently is being developed in grain sorghum and will likely transfer to related weeds. Monitoring the impact of this new nuclear technology on the evolution and invasiveness of related weeds requires a baseline understanding of the population biology of grain sorghum genes once they transfer to in situ weed populations. We previously characterized the rate of gene flow from grain sorghum to shattercane [Sorghum bicolor(L.) Moench nothosubsp.drummondii(Steud.) de Wet ex. Davidse], a conspecific weed relatively common in North America; as well as the ecological fitness of an F1population whenS. bicolornothosubsp.drummondiiwas the maternal parent. Here we report the ecological fitness of aS. bicolornothosubsp.drummondii×S. bicolorssp.bicolorF2population relative to its crop and weed parents. Parental and F2populations were grown in two Nebraska environments in 2012 and 2013. Traits evaluated included overwinter survival, field emergence, biomass production and partitioning at anthesis, total seed production, and 100-seed weight. Results indicated that F2traits were generally intermediate between the parents, but more similar toS. bicolornothosubsp.drummondiithan to grain sorghum. The one exception was overwinter survival, which was nearly 0% for both the F2and the grain sorghum parent in these northern environments. Thus, the frequency of crop alleles stably introgressed intoS. bicolornothosubsp.drummondiipopulations appears to primarily depend on overwinter survival of the F2and which selective pressures are imposed upon it by the cropping system. These data provide needed baseline information about the environmental fate of nuclear genetic technologies deployed in this important global crop.
Plasma Dynamics Associated With Equatorial Ionospheric Irregularities
Authors: Smith Jonathon Matthew , Heelis R. A.
Published: July 2018

The Communication/Navigation Outage Forecasting System satellite was operational from 2008, a period of deep solar minimum, to 2015, a period of moderate solar conditions. The behavior of the vertical plasma drift and the distribution of plasma depletions during the deep solar minimum of 2009 deviated substantially from the behavior that was observed during the solar moderate conditions encountered by the Communication/Navigation Outage Forecasting System satellite in 2014, which are typical of previous observations. Presented here are observations of the vertical drift of plasma depletions and the background plasma in which they are embedded. We find that depletions detected at local times after 2100 hr during solar minimum are typically found in background drifts that are weakly downward compared to the strongly downward background drifts observed during moderate solar activity levels. Additionally, at solar minimum, the drift within the depletions is upward with respect to the background as compared with observations at the same local times during solar moderate conditions for which the depleted plasma more nearly drifts with the background. We note that weak background plasma drifts observed throughout the night during solar minimum promote the continued growth of depletions that may evolve more slowly or be continuously generated to appear in the topside in the postmidnight hours.
Antidiabetic adiponectin receptor agonist AdipoRon suppresses tumour growth of pancreatic cancer by inducing RIPK1/ERK-dependent necroptosis
Authors: Akimoto Miho , Maruyama Riruke , Kawabata Yasunari , Tajima Yoshitsugu , Takenaga Keizo
Published: July 2018

The association between lower circulating adiponectin (APN) levels and the development of pancreatic cancer has been reported. However, the effect of APN on the growth and survival of pancreatic cancer cells remains elusive. Here, we investigate the effects of the anti-diabetic APN receptor (AdipoR) agonist AdipoRon and APN on human pancreatic cancer cells. We found that AdipoRon, but not APN, induces MIAPaCa-2 cell death, mainly through necroptosis. Mechanistically, although both AdipoRon and APN activate AMPK and p38 MAPK in an AdipoR-dependent manner that elicits survival signals, only AdipoRon induces rapid mitochondrial dysfunction through mitochondrial Ca2+ overload, followed by superoxide production via RIPK1 and ERK1/2 activation. Oral administration of AdipoRon suppresses MIAPaCa-2 tumour growth without severe adverse effects and kills cancer cells isolated from patients with pancreatic cancer. Thus, AdipoRon could be a therapeutic agent against pancreatic cancer as well as diabetes.
Combined effects of FH (E404D) and ACOX2 (R409H) cause metabolic defects in primary cardiac malignant tumor
Authors: Zhou Xiangyu , Xu Mengjia , Zeng Weijia , Chen Zhongzhong , Lu Guohui , Gong Yun , Finnell Richard H. , Xiao Huasheng , Qiao Bin , Wang Hongyan
Published: July 2018

Primary malignant cardiac tumors (PMCTs) are extremely rare. The apparent immunity of the heart to invasive cancer has attracted considerable interest given the continuously rising incidence of cancer in other organs. This study aims to determine the conditions that could result in cardiac carcinoma and expand our understanding of cardiac tumor occurrence. We report two cases: a male (Patient-1) with primary cardiac malignant fibrous histiocytoma (MFH) and a female (Patient-2) with primary cardiac angiosarcoma. Merged genome-wide analyses of aCGH, Exome sequencing, and RNA-sequencing were performed on Patient-1 using peripheral blood, carcinoma tissue, and samples of adjacent normal tissue. Only whole-transcriptome analysis was carried out on Patient-2, due to insufficient quantities of sample from Patient-2. We identified a novel inherited loss of functional mutation of FH (Glu404Asp), a recurrent somatic hotspot mutation of PIK3CA (His1047Arg) and a somatic duplication in copy number of HIF1A. FH (E404D) severely compromised FH enzyme activity and lead to decreased protein expression in cardiac tumor tissues. We previously reported a functional mutation ACOX2 (R409H), which is potentially associated with decreased β-oxidation of fatty acids in the cardiac tumor tissue. Results of transcriptome analyses on two patients further revealed that the RNA expression of genes in the TCA cycle and beta-oxidation were uniformly downregulated. In this study, combined effects of FH (E404D) and ACOX2 (R409H) on metabolic switch from fatty acids to glucose were remarkably distinct, which might be an essential precondition to trigger the occurrence of PMCTs and mimic the Warburg effect, a hallmark of cancer metabolism.
Lipid droplet and peroxisome biogenesis occur at the same ER subdomains
Authors: Joshi Amit S. , Nebenfuehr Benjamin , Choudhary Vineet , Satpute-Krishnan Prasanna , Levine Tim P. , Golden Andy , Prinz William A.
Published: July 2018

Nascent lipid droplet (LD) formation occurs in the endoplasmic reticulum (ER) membrane but it is not known how sites of biogenesis are determined. We previously identified ER domains in S. cerevisiae containing the reticulon homology domain (RHD) protein Pex30 that are regions where preperoxisomal vesicles (PPVs) form. Here, we show that Pex30 domains are also sites where most nascent LDs form. Mature LDs usually remain associated with Pex30 subdomains, and the same Pex30 subdomain can simultaneously associate with a LD and a PPV or peroxisome. We find that in higher eukaryotes multiple C2 domain containing transmembrane protein (MCTP2) is similar to Pex30: it contains an RHD and resides in ER domains where most nascent LD biogenesis occurs and that often associate with peroxisomes. Together, these findings indicate that most LDs and PPVs form and remain associated with conserved ER subdomains, and suggest a link between LD and peroxisome biogenesis.
Coherent deglacial changes in western Atlantic Ocean circulation
Authors: Ng Hong Chin , Robinson Laura F. , McManus Jerry F. , Mohamed Kais J. , Jacobel Allison W. , Ivanovic Ruza F. , Gregoire Lauren J. , Chen Tianyu
Published: July 2018

Abrupt climate changes in the past have been attributed to variations in Atlantic Meridional Overturning Circulation (AMOC) strength. However, the exact timing and magnitude of past AMOC shifts remain elusive, which continues to limit our understanding of the driving mechanisms of such climate variability. Here we show a consistent signal of the 231Pa/230Th proxy that reveals a spatially coherent picture of western Atlantic circulation changes over the last deglaciation, during abrupt millennial-scale climate transitions. At the onset of deglaciation, we observe an early slowdown of circulation in the western Atlantic from around 19 to 16.5 thousand years ago (ka), consistent with the timing of accelerated Eurasian ice melting. The subsequent weakened AMOC state persists for over a millennium (~16.5–15 ka), during which time there is substantial ice rafting from the Laurentide ice sheet. This timing indicates a role for melting ice in driving a two-step AMOC slowdown, with a positive feedback sustaining continued iceberg calving and climate change during Heinrich Stadial 1.
Land-use emissions play a critical role in land-based mitigation for Paris climate targets
Authors: Harper Anna B. , Powell Tom , Cox Peter M. , House Joanna , Huntingford Chris , Lenton Timothy M. , Sitch Stephen , Burke Eleanor , Chadburn Sarah E. , Collins William J. , Comyn-Platt Edward , Daioglou Vassilis , Doelman Jonathan C. , Hayman Garry , Robertson Eddy , van Vuuren Detlef , Wiltshire Andy , Webber Christopher P. , Bastos Ana , Boysen Lena , Ciais Philippe , Devaraju Narayanappa , Jain Atul K. , Krause Andreas , Poulter Ben , Shu Shijie
Published: July 2018

Scenarios that limit global warming to below 2 °C by 2100 assume significant land-use change to support large-scale carbon dioxide (CO2) removal from the atmosphere by afforestation/reforestation, avoided deforestation, and Biomass Energy with Carbon Capture and Storage (BECCS). The more ambitious mitigation scenarios require even greater land area for mitigation and/or earlier adoption of CO2 removal strategies. Here we show that additional land-use change to meet a 1.5 °C climate change target could result in net losses of carbon from the land. The effectiveness of BECCS strongly depends on several assumptions related to the choice of biomass, the fate of initial above ground biomass, and the fossil-fuel emissions offset in the energy system. Depending on these factors, carbon removed from the atmosphere through BECCS could easily be offset by losses due to land-use change. If BECCS involves replacing high-carbon content ecosystems with crops, then forest-based mitigation could be more efficient for atmospheric CO2 removal than BECCS.
A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma
Authors: Chen Xiaoyue , Zhang Minjie , Gan Haiyun , Wang Heping , Lee Jeong-Heon , Fang Dong , Kitange Gaspar J. , He Lihong , Hu Zeng , Parney Ian F. , Meyer Fredric B. , Giannini Caterina , Sarkaria Jann N. , Zhang Zhiguo
Published: July 2018

Temozolomide (TMZ) was used for the treatment of glioblastoma (GBM) for over a decade, but its treatment benefits are limited by acquired resistance, a process that remains incompletely understood. Here we report that an enhancer, located between the promoters of marker of proliferation Ki67 (MKI67) and O6-methylguanine-DNA-methyltransferase (MGMT) genes, is activated in TMZ-resistant patient-derived xenograft (PDX) lines and recurrent tumor samples. Activation of the enhancer correlates with increased MGMT expression, a major known mechanism for TMZ resistance. We show that forced activation of the enhancer in cell lines with low MGMT expression results in elevated MGMT expression. Deletion of this enhancer in cell lines with high MGMT expression leads to a dramatic reduction of MGMT and a lesser extent of Ki67 expression, increased TMZ sensitivity, and impaired proliferation. Together, these studies uncover a mechanism that regulates MGMT expression, confers TMZ resistance, and potentially regulates tumor proliferation.
Author Correction: The State of the World’s Beaches
Authors: Luijendijk Arjen , Hagenaars Gerben , Ranasinghe Roshanka , Baart Fedor , Donchyts Gennadii , Aarninkhof Stefan
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Precoce and opposite response of proteasome activity after acute or chronic exposure of C. elegans to γ-radiation
Authors: Dubois Cécile , Lecomte Catherine , Ruys Sébastien Pyr dit , Kuzmic Mira , Della-Vedova Claire , Dubourg Nicolas , Galas Simon , Frelon Sandrine
Published: July 2018

Species are chronically exposed to ionizing radiation, a natural phenomenon which can be enhanced by human activities. The induced toxicity mechanisms still remain unclear and seem depending on the mode of exposure, i.e. acute and chronic. To better understand these phenomena, studies need to be conducted both at the subcellular and individual levels. Proteins, functional molecules in organisms, are the targets of oxidative damage (especially via their carbonylation (PC)) and are likely to be relevant biomarkers. After exposure of Caenorhabditis elegans to either chronic or acute γ rays we showed that hatching success is impacted after acute but not after chronic irradiation. At the molecular level, the carbonylated protein level in relation with dose was slightly different between acute and chronic exposure whereas the proteolytic activity is drastically modified. Indeed, whereas the 20S proteasome activity is inhibited by acute irradiation from 0.5 Gy, it is activated after chronic irradiation from 1 Gy. As expected, the 20S proteasome activity is mainly modified by irradiation whereas the 26S and 30S activity are less changed. This study provides preliminaries clues to understand the role of protein oxidation and proteolytic activity in the radiation-induced molecular mechanisms after chronic versus acute irradiation in C. elegans.
Annatto-extracted tocotrienols improve glucose homeostasis and bone properties in high-fat diet-induced type 2 diabetic mice by decreasing the inflammatory response
Authors: Shen Chwan-Li , Kaur Gurvinder , Wanders Desiree , Sharma Shaligram , Tomison Michael D. , Ramalingam Latha , Chung Eunhee , Moustaid-Moussa Naima , Mo Huanbiao , Dufour Jannette M.
Published: July 2018

Diabetes is a risk factor for osteoporosis. Annatto-extracted tocotrienols (TT) have proven benefits in preserving bone matrix. Here, we evaluated the effects of dietary TT on glucose homeostasis, bone properties, and liver pro-inflammatory mRNA expression in high-fat diet (HFD)-induced type 2 diabetic (T2DM) mice. 58 male C57BL/6 J mice were divided into 5 groups: low-fat diet (LFD), HFD, HFD + 400 mgTT/kg diet (T400), HFD + 1600 mgTT/kg diet (T1600), and HFD + 200 mg metformin/kg (Met) for 14 weeks. Relative to the HFD group, both TT-supplemented groups (1) improved glucose homeostasis by lowering the area under the curve for both glucose tolerance and insulin tolerance tests, (2) increased serum procollagen I intact N-terminal propeptide (bone formation) level, trabecular bone volume/total volume, trabecular number, connectivity density, and cortical thickness, (3) decreased collagen type 1 cross-linked C-telopeptide (bone resorption) levels, trabecular separation, and structure model index, and (4) suppressed liver mRNA levels of inflammation markers including IL-2, IL-23, IFN-γ, MCP-1, TNF-α, ITGAX and F4/80. There were no differences in glucose homeostasis and liver mRNA expression among T400, T1600, and Met. The order of osteo-protective effects was LFD ≥T1600 ≥T400 = Met >HFD. Collectively, these data suggest that TT exerts osteo-protective effects in T2DM mice by regulating glucose homeostasis and suppressing inflammation.
Greenland ice mass loss during the Younger Dryas driven by Atlantic Meridional Overturning Circulation feedbacks
Authors: Rainsley Eleanor , Menviel Laurie , Fogwill Christopher J. , Turney Chris S. M. , Hughes Anna L. C. , Rood Dylan H.
Published: July 2018

Understanding feedbacks between the Greenland Ice Sheet (GrIS) and the Atlantic Meridional Overturning Circulation (AMOC) is crucial for reducing uncertainties over future sea level and ocean circulation change. Reconstructing past GrIS dynamics can extend the observational record and elucidate mechanisms that operate on multi-decadal timescales. We report a highly-constrained last glacial vertical profile of cosmogenic isotope exposure ages from Sermilik Fjord, a marine-terminating ice stream in the southeast sector of the GrIS. Our reconstruction reveals substantial ice-mass loss throughout the Younger Dryas (12.9-11.7 ka), a period of marked atmospheric and sea-surface cooling. Earth-system modelling reveals that southern GrIS marginal melt was likely driven by strengthening of the Irminger Current at depth due to a weakening of the AMOC during the Younger Dryas. This change in North Atlantic circulation appears to have drawn warm subsurface waters to southeast Greenland despite markedly cooler sea surface temperatures, enhancing thermal erosion at the grounding lines of palaeo ice-streams, supporting interpretation of regional marine-sediment cores. Given current rates of GrIS meltwater input into the North Atlantic and the vulnerability of major ice streams to water temperature changes at the grounding line, this mechanism has important implications for future AMOC changes and northern hemisphere heat transport.
Ocean acidification drives community shifts towards simplified non-calcified habitats in a subtropical−temperate transition zone
Authors: Agostini Sylvain , Harvey Ben P. , Wada Shigeki , Kon Koetsu , Milazzo Marco , Inaba Kazuo , Hall-Spencer Jason M.
Published: July 2018

Rising atmospheric concentrations of carbon dioxide are causing surface seawater pH and carbonate ion concentrations to fall in a process known as ocean acidification. To assess the likely ecological effects of ocean acidification we compared intertidal and subtidal marine communities at increasing levels of pCO2 at recently discovered volcanic seeps off the Pacific coast of Japan (34° N). This study region is of particular interest for ocean acidification research as it has naturally low levels of surface seawater pCO2 (280–320 µatm) and is located at a transition zone between temperate and sub-tropical communities. We provide the first assessment of ocean acidification effects at a biogeographic boundary. Marine communities exposed to mean levels of pCO2 predicted by 2050 experienced periods of low aragonite saturation and high dissolved inorganic carbon. These two factors combined to cause marked community shifts and a major decline in biodiversity, including the loss of key habitat-forming species, with even more extreme community changes expected by 2100. Our results provide empirical evidence that near-future levels of pCO2 shift sub-tropical ecosystems from carbonate to fleshy algal dominated systems, accompanied by biodiversity loss and major simplification of the ecosystem.
Blast exposure elicits blood-brain barrier disruption and repair mediated by tight junction integrity and nitric oxide dependent processes
Authors: Logsdon Aric F. , Meabon James S. , Cline Marcella M. , Bullock Kristin M. , Raskind Murray A. , Peskind Elaine R. , Banks William A. , Cook David G.
Published: July 2018

Mild blast-induced traumatic brain injury (TBI) is associated with blood-brain barrier (BBB) disruption. However, the mechanisms whereby blast disrupts BBB integrity are not well understood. To address this issue BBB permeability to peripherally injected 14C-sucrose and 99mTc-albumin was quantified in ten brain regions at time points ranging from 0.25 to 72 hours. In mice, repetitive (2X) blast provoked BBB permeability to 14C-sucrose that persisted in specific brain regions from 0.25 to 72 hours. However, 99mTc-albumin revealed biphasic BBB disruption (open-closed-open) over the same interval, which was most pronounced in frontal cortex and hippocampus. This indicates that blast initiates interacting BBB disruption and reparative processes in specific brain regions. Further investigation of delayed (72 hour) BBB disruption revealed that claudin-5 (CLD5) expression was disrupted specifically in the hippocampus, but not in dorsal striatum, a brain region that showed no blast-induced BBB permeability to sucrose or albumin. In addition, we found that delayed BBB permeability and disrupted CLD5 expression were blocked by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). These data argue that latent nitric oxide-dependent signaling pathways initiate processes that result in delayed BBB disruption, which are manifested in a brain-region specific manner.
Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression
Authors: Cho Sungrae , Chae Jin Sung , Shin Hocheol , Shin Yujeong , Song Haeun , Kim Youngwook , Yoo Byong Chul , Roh Kangsan , Cho Seungchan , Kil Eui-joon , Byun Hee-seong , Cho Sang-ho , Park Seyeon , Lee Sukchan , Yeom Chang-Hwan
Published: July 2018

L-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of L-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of L-ascorbic acid. In this study, we demonstrate that L-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of L-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose L-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose L-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of L-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that L-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.
Validating Antibodies for Quantitative Western Blot Measurements with Microwestern Array
Authors: Koch Rick J. , Barrette Anne Marie , Stern Alan D. , Hu Bin , Bouhaddou Mehdi , Azeloglu Evren U. , Iyengar Ravi , Birtwistle Marc R.
Published: July 2018

Fluorescence-based western blots are quantitative in principal, but require determining linear range for each antibody. Here, we use microwestern array to rapidly evaluate suitable conditions for quantitative western blotting, with up to 192 antibody/dilution/replicate combinations on a single standard size gel with a seven-point, two-fold lysate dilution series (~100-fold range). Pilot experiments demonstrate a high proportion of investigated antibodies (17/24) are suitable for quantitative use; however this sample of antibodies is not yet comprehensive across companies, molecular weights, and other important antibody properties, so the ubiquity of this property cannot yet be determined. In some cases microwestern struggled with higher molecular weight membrane proteins, so the technique may not be uniformly applicable to all validation tasks. Linear range for all validated antibodies is at least 8-fold, and up to two orders of magnitude. Phospho-specific and total antibodies do not have discernable trend differences in linear range or limit of detection. Total antibodies generally required higher working concentrations, but more comprehensive antibody panels are required to better establish whether this trend is general or not. Importantly, we demonstrate that results from microwestern analyses scale to normal “macro” western for a subset of antibodies.
Transcriptomic Analysis of Hepatic Cells in Multicellular Organotypic Liver Models
Authors: Tegge Allison N. , Rodrigues Richard R. , Larkin Adam L. , Vu Lucas , Murali T. M. , Rajagopalan Padmavathy
Published: July 2018

Liver homeostasis requires the presence of both parenchymal and non-parenchymal cells (NPCs). However, systems biology studies of the liver have primarily focused on hepatocytes. Using an organotypic three-dimensional (3D) hepatic culture, we report the first transcriptomic study of liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) cultured with hepatocytes. Through computational pathway and interaction network analyses, we demonstrate that hepatocytes, LSECs and KCs have distinct expression profiles and functional characteristics. Our results show that LSECs in the presence of KCs exhibit decreased expression of focal adhesion kinase (FAK) signaling, a pathway linked to LSEC dedifferentiation. We report the novel result that peroxisome proliferator-activated receptor alpha (PPARα) is transcribed in LSECs. The expression of downstream processes corroborates active PPARα signaling in LSECs. We uncover transcriptional evidence in LSECs for a feedback mechanism between PPARα and farnesoid X-activated receptor (FXR) that maintains bile acid homeostasis; previously, this feedback was known occur only in HepG2 cells. We demonstrate that KCs in 3D liver models display expression patterns consistent with an anti-inflammatory phenotype when compared to monocultures. These results highlight the distinct roles of LSECs and KCs in maintaining liver function and emphasize the need for additional mechanistic studies of NPCs in addition to hepatocytes in liver-mimetic microenvironments.