bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of Renal (Pro)Renin Receptor Contributes to High Fructose-Induced Salt Sensitivity
Authors: Xu Chuanming , Lu Aihua , Lu Xiaohan , Zhang Linlin , Fang Hui , Zhou Li , Yang Tianxin
Published: December 2016

A high-fructose diet is shown to induce salt-sensitive hypertension, but the underlying mechanism largely remains unknown. The major goal of the present study was to test the role of renal (pro)renin receptor (PRR) in this model. In Sprague–Dawley rats, high-fructose intake increased renal expression of full-length PRR, which were attenuated by allopurinol. High-fructose intake also upregulated renal mRNA and protein expression of sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter, as well as in vivo Na/K/2Cl cotransporter activity, all of which were nearly completely blocked by a PRR decoy inhibitor PRO20 or allopurinol treatment. Parallel changes were observed for indices of intrarenal renin–angiotensin–system including renal and urinary renin and angiotensin II levels. Radiotelemetry demonstrated that high-fructose or a high-salt diet alone did not affect mean arterial pressure, but the combination of the 2 maneuvers induced a ≈10-mm Hg increase of mean arterial pressure, which was blunted by PRO20 or allopurinol treatment. In cultured human kidney 2 cells, both fructose and uric acid increased protein expression of soluble PRR in a time- and dose-dependent manner; fructose-induced PRR upregulation was inhibited by allopurinol. Taken together, our data suggest that fructose via uric acid stimulates renal expression of PRR/soluble PRR that stimulate sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter expression and intrarenal renin–angiotensin system to induce salt-sensitive hypertension.
Arterial Stiffness and Risk of Overall Heart Failure, Heart Failure With Preserved Ejection Fraction, and Heart Failure With Reduced Ejection Fraction
Authors: Pandey Ambarish , Khan Hassan , Newman Anne B. , Lakatta Edward G. , Forman Daniel E. , Butler Javed , Berry Jarett D.
Published: December 2016

Higher arterial stiffness is associated with increased risk of atherosclerotic events. However, its contribution toward risk of heart failure (HF) and its subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), independent of other risk factors is not well established. In this study, we included Health ABC study (Health, Aging, and Body Composition) participants without prevalent HF who had arterial stiffness measured as carotid–femoral pulse wave velocity (cf-PWV) at baseline (n=2290). Adjusted Cox-proportional hazards models were constructed to determine the association between continuous and data-derived categorical measures (tertiles) of cf-PWV and incidence of HF and its subtypes (HFpEF [ejection fraction >45%] and HFrEF [ejection fraction ≤45%]). We observed 390 HF events (162 HFpEF and 145 HFrEF events) over 11.4 years of follow-up. In adjusted analysis, higher cf-PWV was associated with greater risk of HF after adjustment for age, sex, ethnicity, mean arterial pressure, and heart rate (hazard ratio [95% confidence interval] for cf-PWV tertile 3 versus tertile 1 [ref] =1.35 [1.05–1.73]). However, this association was not significant after additional adjustment for other cardiovascular risk factors (hazard ratio [95% confidence interval], 1.14 [0.88–1.47]). cf-PWV velocity was also not associated with risk of HFpEF and HFrEF after adjustment for potential confounders (most adjusted hazard ratio [95% confidence interval] for cf-PWV tertile 3 versus tertile 1 [ref]: HFpEF, 1.06 [0.72–1.56]; HFrEF, 1.28 [0.83–1.97]). In conclusion, arterial stiffness, as measured by cf-PWV, is not independently associated with risk of HF or its subtypes after adjustment for traditional cardiovascular risk factors.
Secondhand Smoke Exposure and Subclinical Cardiovascular Disease: The Multi‐Ethnic Study of Atherosclerosis
Authors: Jones Miranda R. , Magid Hoda S. , Al‐Rifai Mahmoud , McEvoy John W. , Kaufman Joel D. , Hinckley Stukovsky Karen D. , Szklo Moyses , Polak Joseph , Burke Gregory L. , Post Wendy S. , Blaha Michael J. , Navas‐Acien Ana
Published: December 2016

Background

Few studies have evaluated the association between secondhand smoke (
SHS
) and subclinical cardiovascular disease among ethnically diverse populations. This study assesses the impact of
SHS
on inflammation and atherosclerosis (carotid intima‐media thickness, coronary artery calcification, and peripheral arterial disease).

Methods and Results

We examined 5032 nonsmoking adults aged 45 to 84 years without prior cardiovascular disease participating in the Multi‐Ethnic Study of Atherosclerosis (
MESA
) from 2000 to 2002.
SHS
exposure was determined by self‐report, and urinary cotinine was measured in a representative subset (n=2893). The multi‐adjusted geometric mean ratios (95% CIs) for high‐sensitivity C‐reactive protein and interleukin‐6 comparing 407 participants with
SHS
≥12 h/wk versus 3035 unexposed participants were 1.13 (1.02–1.26) and 1.04 (0.98–1.11), respectively. The multi‐adjusted geometric mean ratio for carotid intima‐media thickness was 1.02 (0.97–1.07). Fibrinogen and coronary artery calcification were not associated with
SHS
. The prevalence of peripheral arterial disease (ankle‐brachial index ≤0.9 or ≥1.4) was associated with detectable urinary cotinine (odds ratio, 2.10; 95% CI, 1.09–4.04) but not with self‐reported
SHS
. Urinary cotinine was not associated with inflammation or carotid intima‐media thickness.

Conclusions

Despite limited exposure assessment, this study supports the association of
SHS
exposure with inflammation and peripheral arterial disease.
Relationship Between Endothelial Wall Shear Stress and High‐Risk Atherosclerotic Plaque Characteristics for Identification of Coronary Lesions That Cause Ischemia: A Direct Comparison With Fractional Flow Reserve
Authors: Han Donghee , Starikov Anna , ó Hartaigh Bríain , Gransar Heidi , Kolli Kranthi K. , Lee Ji Hyun , Rizvi Asim , Baskaran Lohendran , Schulman‐Marcus Joshua , Lin Fay Y. , Min James K.
Published: December 2016

Background

Wall shear stress (
WSS
) is an established predictor of coronary atherosclerosis progression. Prior studies have reported that high
WSS
has been associated with high‐risk atherosclerotic plaque characteristics (
APC
s).
WSS
and
APC
s are quantifiable by coronary computed tomography angiography, but the relationship of coronary lesion ischemia—evaluated by fractional flow reserve—to
WSS
and
APC
s has not been examined.

Methods and Results

WSS
measures were obtained from 100 evaluable patients who underwent coronary computed tomography angiography and invasive coronary angiography with fractional flow reserve. Patients were categorized according to tertiles of mean
WSS
values defined as low, intermediate, and high. Coronary ischemia was defined as fractional flow reserve ≤0.80. Stenosis severity was determined by minimal luminal diameter.
APC
s were defined as positive remodeling, low attenuation plaque, and spotty calcification. The likelihood of having positive remodeling and low‐attenuation plaque was greater in the high
WSS
group compared with the low
WSS
group after adjusting for minimal luminal diameter (odds ratio for positive remodeling: 2.54, 95%
CI
1.12–5.77; odds ratio for low‐attenuation plaque: 2.68, 95%
CI
1.02–7.06; both
P
<0.05). No significant relationship was observed between
WSS
and fractional flow reserve when adjusting for either minimal luminal diameter or
APC
s.
WSS
displayed no incremental benefit above stenosis severity and
APC
s for detecting lesions that caused ischemia (area under the curve for stenosis and
APC
s: 0.87, 95%
CI
0.81–0.93; area under the curve for stenosis,
APC
s, and
WSS
: 0.88, 95%
CI
0.82–0.93;
P
=0.30 for difference).

Conclusions

High
WSS
is associated with
APC
s independent of stenosis severity.
WSS
provided no added value beyond stenosis severity and
APC
s for detecting lesions with significant ischemia.
Grotius, Informal Empire and the Conclusion of Unequal Treaties
Authors: Van Hulle Inge
Published: December 2016

Unequal treaties have become synonymous with the imperial practice of Western states in East Asia during the nineteenth century. They have also become a popular subject of study for historians of international law. A neglected feature of the history of unequal treaties is the way they were used and theorised upon as instruments of informal empire before the nineteenth century, in the early-modern age. Hugo Grotius in particular wrote extensively on unequal treaties and alliances through his familiarity with the Dutch East India Company’s exploits in the East Indies, where the conclusion of treaties with indigenous rulers formed the cornerstone of Dutch imperialism. This article delves into the early-modern roots of unequal alliances and discusses how the Grotian analysis of unequal alliances influenced other authors of the classic law of nations.
Hugo Grotius’s Hermeneutics of Natural and Divine Law
Authors: Ertz Stefanie
Published: December 2016

Interchanges between political, juridical and theological thought in the early modern period have been studied extensively during the past decades. Less light has been cast on the corresponding interrelations between politico-juridical thought and biblical hermeneutics. However, this issue deserves some attention, too, as the following case study on Hugo Grotius wants to show by pointing to the mutual adjustment of juridical, theological and biblical arguments in the progress of the core semantics of Grotius’s natural law theory from De iure praedae to De iure belli ac pacis.
The Role of Kinship in Negotiating Territorial Rights
Authors: Ahearn Ariell
Published: December 2016

This paper explores the role of kinship in herder claims for winter shelter ownership in rural Mongolia, where pastureland is currently designated as state-owned property in the national constitution. Drawing on ethnographic research conducted amongst mobile pastoralist households, this article demonstrates how contemporary winter pasture rights take shape within a locus of political relations structured by custodial land-use practices. It highlights the ways that herders negotiate for territorial rights through appeals to established regional families and are how these appeals are mediated by local government administration. From this analysis, I argue that concepts of kinship in the political economy of pastoralism should be re-examined in light of current debates around land-tenure legislation in Mongolia.
間接題元語義地圖之修訂及其在漢語比較語法與歷史語法研究中的作用
Authors: Zhang Min
Published: December 2016

This paper presents a revised version of the semantic map for oblique roles originally proposed by Haspelmath (2003) for instrumental and related functions and expanded by M. Zhang (M. Zhang 2008a, 2010) to accommodate more roles, particularly the Chinese-specific oblique role generally known among Chinese linguists aschùzhìshì shòushì處置式受事 “pretransitive/disposal patient.” My purpose is twofold: (1) to demonstrate the usefulness of a “bottom-up” approach to the semantic map model as an innovative tool for the study of comparative Chinese dialectal and diachronic grammar; and (2) to discuss particular issues pertaining to the construction and revision of the oblique-role map, and to illustrate how such a map can contribute to our understanding of the typology and diachrony of oblique markers across regional varieties of Chinese.

為確定漢語特有的「處置式受事」角色的類型學地位，筆者（張敏2008–2010）曾將  Haspelmath（2003）提出的工具語及相關功能語義地圖擴充為一個初步的間接題元語義地圖。本文對該圖作出進一步修訂,旨在（1）為漢語方言比較語法和歷史語法學界推介一種簡便易行的「自下而上」的語義地圖建構方法，（2）探討間接題元語義地圖建構及修訂中遇到的一些疑難問題，並說明該圖在漢語方言間接題元標記的共時及歷時研究中的作用。(This article is in English.)
海南閩語結果結構
Authors: Lee Hui-chi
Published: December 2016

This paper introduces the resultative constructions in Hainan Min which have not been seriously examined in previous studies. The serial verb construction (SVC) is the main mechanism by which resultatives are expressed in Hainan Min. This special syntactic structure is examined in Hainan Min and compared to two other Chinese dialects: Taiwan Southern Min and Cantonese. I speculate that the unusual serial verb construction resultatives are associated with the preservation of a historical form and language contact. Diachronic Chinese data are given to evince thatSVCs existed early in archaic Chinese. In addition, it is argued that language contact with the native language (Hlai) also contributes to the preservation of this historic remnant.

本文介紹海南閩語的結果結構。這個語法結構在過去的文獻中並未清楚的描述及討論過。本研究使用的材料大多是作者田野調查後的語料。田調的結果發現，海南閩語的結果結構主要是以連動結構來表現。以連動結構來表達結果，在現代漢語中，是一種很特殊的方式。本文因此比較了相關的漢語方言：台灣閩南語及粵語。同時，還考察了古漢語的歷時語料，發現連動結果句型應是一種存古現象。除了歷史因素外，本文還主張語言接觸也影響了連動結果句型的存古。因此，本文還探討了海南島上的黎語之結果結構。(This article is in English.)
廣西欽州漢佬話的語言成分來源及詞彙整合
Authors: Luo Yuyan
Published: December 2016

The Hanlao language in Qinzhou city of Guangxi Province is a language blending the Zhuang language and Han dialects. The part of Han comes mainly from Cantonese, Pinghua and Hakka. Different source dialects influence Hanlao in distinctive levels. The core vocabulary of Hanlao language is mainly influenced by Zhuang, the influence of which becoming weaker towards the periphery. On the contrary, the Han dialects mainly affect the peripheral words of the Hanlao language. Hanlao thus obtains its present form through the restructuring of various source languages in a complex way.

廣西欽州漢佬話是一種融合壯語、漢語的語言，漢語主要來自粵語、平話和客家話。各種來源語言在漢佬話中所處的地位不同：壯語的影響主要在核心詞部分，越往外圍影響越小；漢語則相反，核心詞部分影響小，越往外圍影響越大。各種來源語言經過了複雜的整合過程形成了漢佬話如今的面貌。(This article is in Chinese.)
A new record and two new species of Cryptochironomus Kieffer, 1918 from China (Diptera, Chironomidae)
Authors: YAN CHUNCAI , ZHAO GUANGJUN , LIU TING , GUO QIN , HOU ZIYUAN , WANG XINHUA , PAN BAOPING
Published: December 2016

Two new species of the genus Cryptochironomus Kieffer, C. maculus Yan & Wang sp. n. and C. protuberans Yan & Wang sp. n. are described and illustrated as adult males. C. albofasciatus (Staeger) is recorded from China for the first time. A key to the males of Cryptochironomus in China is presented and generic diagnosis is emended.
Evaluating Four Remote Sensing Methods for Estimating Surface Air Temperature on a Regional Scale
Authors: Liu Suhua , Su Hongbo , Tian Jing , Zhang Renhua , Wang Weizhen , Wu Yueru
Published: December 2016

Surface air temperature is a basic meteorological variable to monitor the environment and assess climate change. Four remote sensing methods—the temperature–vegetation index (TVX), the univariate linear regression method, the multivariate linear regression method, and the advection-energy balance for surface air temperature (ADEBAT)—have been developed to acquire surface air temperature on a regional scale. To evaluate their utilities, they were applied to estimate the surface air temperature in northwestern China and were compared with each other through regressive analyses, t tests, estimation errors, and analyses on estimations of different underlying surfaces. Results can be summarized into three aspects: 1) The regressive analyses and t tests indicate that the multivariate linear regression method and the ADEBAT provide better accuracy than the other two methods. 2) Frequency histograms on estimation errors show that the multivariate linear regression method produces the minimum error range, and the univariate linear regression method produces the maximum error range. Errors of the multivariate linear regression method exhibit a nearly normal distribution and that of the ADEBAT exhibit a bimodal distribution, whereas the other two methods display negative skewness distributions. 3) Estimates on different underlying surfaces show that the TVX and the univariate linear regression method are significantly limited in regions with sparse vegetation cover. The multivariate linear regression method has estimation errors within 1°C and without high levels of errors, and the ADEBAT also produces high estimation errors on bare ground.
A Numerical Study on Rapid Intensification of Typhoon Vicente (2012) in the South China Sea. Part I: Verification of Simulation, Storm-Scale Evolution, and Environmental Contribution
Authors: Chen Xiaomin , Wang Yuqing , Zhao Kun , Wu Dan
Published: December 2016

Typhoon Vicente (2012) underwent an extreme rapid intensification (RI) over the northern South China Sea just before its landfall in south China. The extreme RI, the sudden track deflection, and the inner- and outer-core structures of Vicente were reasonably reproduced in an Advanced Research version of the Weather Research and Forecasting (WRF-ARW) Model simulation. The evolutions of the axisymmetric inner-core radar reflectivity and the primary circulation of the simulated Vicente before its landfall were verified against the Doppler radar observations.

Two intensification stages were identified: 1) the asymmetric intensification stage (i.e., RI onset), represented by a relatively slow intensification rate accompanied by a distinct eyewall contraction; and 2) the axisymmetric RI stage with very slow eyewall contraction. Results from a storm-scale tangential wind tendency budget indicated that the primary spinup mechanism during the first stage was the radial eddy momentum transport, which was beneficial to accelerate primary circulation inside the radius of maximum wind (RMW) and thus conducive to eyewall contraction. In contrast, the principal spinup mechanism during the second stage was mainly ascribed to the forced secondary circulation in response to diabatic heating in the eyewall and boundary layer friction, which efficiently transported the absolute angular momentum radially inward and vertically upward to increase the primary circulation in the eyewall region throughout the troposphere. Further analysis revealed that the interaction between the monsoon circulation and storm-scale vorticity anomalies played an important role in erecting the tilted vortex and spinning up the midtropospheric TC circulation during the first stage.
Climate Events and Impact on Cropping Activities of Small-Scale Farmers in a Part of Southwest Nigeria
Authors: Eludoyin Adebayo Oluwole , Nevo Augustina Olichikwu , Abuloye Peter Adeolu , Eludoyin Oyenike Mary , Awotoye Olusegun Olufemi
Published: December 2016

The study examined the variations of selected climatic variables (rainfall and temperature) and the perceptions of small-scale farmers on the effects of extreme climate condition on cropping activities in the rain forest ecological region in southwest Nigeria. The area is characterized by three different subecological strata (the mountainous Akoko region in the north, the southern coastal area, and the middle, relatively lowland and more urbanized area) whose effects on the climate are made explicit in the relatively different values of the climate variables. Analysis of the responses to questions on perceptions of extreme climate effects indicated that about 70% of the farmers were aware of the effects of extreme climate events on crop production and yield, and over 50% indicated that too early rainfall, late rainfall, prolonged dryness after an initial rainfall, excessive rainfall, and windstorms were the common weather-related causes of low crop yields. More than 76% of the farmers changed planting dates and diversified their crops as mitigation measures, while about 72% adopted mulching and intercropping as adaptation strategies against extreme weather conditions. Only less than 20% had access to government support facilities and modern infrastructure. The study concluded that although the farmers respond to variable and extreme climate events in the study area, the responses, being not adequately supported by adequate farming infrastructure, do not guarantee sustainable food security in the region.
acdc – Automated Contamination Detection and Confidence estimation for single-cell genome data
Authors: Lux Markus , Krüger Jan , Rinke Christian , Maus Irena , Schlüter Andreas , Woyke Tanja , Sczyrba Alexander , Hammer Barbara
Published: December 2016

Background

A major obstacle in single-cell sequencing is sample contamination with foreign DNA. To guarantee clean genome assemblies and to prevent the introduction of contamination into public databases, considerable quality control efforts are put into post-sequencing analysis. Contamination screening generally relies on reference-based methods such as database alignment or marker gene search, which limits the set of detectable contaminants to organisms with closely related reference species. As genomic coverage in the tree of life is highly fragmented, there is an urgent need for a reference-free methodology for contaminant identification in sequence data.

Results

We present acdc, a tool specifically developed to aid the quality control process of genomic sequence data. By combining supervised and unsupervised methods, it reliably detects both known and de novo contaminants. First, 16S rRNA gene prediction and the inclusion of ultrafast exact alignment techniques allow sequence classification using existing knowledge from databases. Second, reference-free inspection is enabled by the use of state-of-the-art machine learning techniques that include fast, non-linear dimensionality reduction of oligonucleotide signatures and subsequent clustering algorithms that automatically estimate the number of clusters. The latter also enables the removal of any contaminant, yielding a clean sample. Furthermore, given the data complexity and the ill-posedness of clustering, acdc employs bootstrapping techniques to provide statistically profound confidence values. Tested on a large number of samples from diverse sequencing projects, our software is able to quickly and accurately identify contamination. Results are displayed in an interactive user interface. Acdc can be run from the web as well as a dedicated command line application, which allows easy integration into large sequencing project analysis workflows.

Conclusions

Acdc can reliably detect contamination in single-cell genome data. In addition to database-driven detection, it complements existing tools by its unsupervised techniques, which allow for the detection of de novo contaminants. Our contribution has the potential to drastically reduce the amount of resources put into these processes, particularly in the context of limited availability of reference species. As single-cell genome data continues to grow rapidly, acdc adds to the toolkit of crucial quality assurance tools.
The legacies of slavery in and out of Africa
Authors: Bertocchi Graziella
Published: December 2016

The slave trades out of Africa represent one of the most significant forced migration experiences in history. In this paper, I illustrate their long-term consequences on contemporaneous socio-economic outcomes, drawing from my own previous work on the topic and from an extensive review of the available literature. I first consider the influence of the slave trade on the “sending” countries in Africa, with attention to their economic, institutional, demographic, and social implications. Next, I evaluate the consequences of the slave trade on the “receiving” countries in the Americas. Here, I distinguish between the case of Latin America and that of the USA. Overall, I show that the slave trades exert a lasting impact along several contemporaneous socio-economic dimensions and across diverse areas of the world.

JEL Classification:J47, J15, O15, N30, P48, Z10
Efficient gravity inversion of basement relief using a versatile modeling algorithm
Authors: Silva João B. C. , Santos Darcicléa F.
Published: December 2016

We have developed a novel approach to compute, in an efficient and versatile way, the gravity anomaly produced by an arbitrary, discrete 3D distribution of density contrast. The method allows adjustable precision and is particularly suited for the interpretation of sedimentary basins. Because the gravity field decays with the square of the distance, we use a discrete Green’s operator that may be made much smaller than the whole study area. For irregularly positioned observations, this discrete Green’s operator must be computed just at the first iteration, and because each of its horizontal layers presents a center of symmetry, only one-eighth of its total elements need to be calculated. Furthermore, for gridded data on a plane, this operator develops translation symmetry for the whole region of interest and has to be computed just once for a single arbitrary observation position. The gravity anomaly is obtained as the product of this small operator by any arbitrary density contrast distribution in a convolution-like operation. We use the proposed modeling to estimate the basement relief of a [Formula: see text] basin with density contrast varying along [Formula: see text] only using a smaller Green’s operator at all iterations. The median of the absolute differences between relief estimates, using the small and a large operator (the latter covering the whole basin) has been approximately 9 m for a 3.6 km deep basin. We also successfully inverted the anomaly of a simulated basin with density contrast varying laterally and vertically, and a real anomaly produced by a steeply dipping basement. The proposed modeling is very fast. For 10,000 observations gridded on a plane, the inversion using the proposed approach for irregularly spaced data is two orders of magnitude faster than using an analytically derived fitting, and this ratio increases enormously with the number of observations.
Signal extraction using randomized-order multichannel singular spectrum analysis
Authors: Huang Weilin , Wang Runqiu , Yuan Yimin , Gan Shuwei , Chen Yangkang
Published: December 2016

Multichannel singular spectrum analysis (MSSA) is an effective algorithm for random noise attenuation; however, it cannot be used to suppress coherent noise. This limitation results from the fact that the conventional MSSA method cannot distinguish between useful signals and coherent noise in the singular spectrum. We have developed a randomization operator to disperse the energy of the coherent noise in the time-space domain. Furthermore, we have developed a novel algorithm for the extraction of useful signals, i.e., for simultaneous random and coherent noise attenuation, by introducing a randomization operator into the conventional MSSA algorithm. In this method, which we call randomized-order MSSA, the traces along the trajectory of each signal component are randomly rearranged. Two ways to extract the trajectories of different signal components are investigated. The first is based on picking the extrema of the upper envelopes, a method that is also constrained by local and global gradients. The second is based on dip scanning in local processing windows, also known as the Radon method. The proposed algorithm can be applied in 2D and 3D data sets to extract different coherent signal components or to attenuate ground roll and multiples. Different synthetic and field data examples demonstrate the successful performance of the proposed method.
Using Open-Access Data in the Development of Exposure Data Sets of Industrial Buildings for Earthquake Risk Modeling
Authors: Sousa Luis , Silva Vitor , Bazzurro Paolo
Published: December 2016

Recent developments in volunteered geographic information (VGI), such as the OpenStreetMap initiative, highlight the potential of these data sets as supplementary or alternative sources of spatially based building information. Its increase in usefulness is particularly evident when combined with additional open-access data, such as the CORINE initiative, which provides the geo-referenced distribution of non-residential areas in Europe. However, the systematic application of VGI in the development of exposure models for catastrophe risk assessment has been the subject of limited research. In this paper, we describe an algorithm that, based on open-access information, provides an automated tool for the development of exposure data sets of industrial buildings in Europe, at the 30 arc-second resolution. Its practical application shows that results obtained at national and regional scales are in excellent agreement with data collected from cadastral agencies in Denmark, Italy, and Portugal; which highlights the potential of the algorithm when real building information is scarce or non-existent.
Introduction: To Support Our Claims
Authors: Bynum Caroline Walker , Doyno Mary Harvey , von Mücke Dorothea , Paxton Frederick S. , Naddaff Ramona , Wallerstein Katharine
Published: December 2016

The historian Caroline Walker Bynum, who solicited and organized this set of five case studies, explains in her introduction to them that their intent is to bypass the currently popular and unsupported claim that the humanities have practical relevance and, instead, to offer ruminative descriptions of what happens when teachers and students meet to discuss texts and objects. She explains that the essays report in detail on five individual classes in five very different academic settings, in the hope of helping to turn the international anglophone conversation about humanistic education away from utilitarian, presentist, all-inclusive claims and toward a demonstration of what the humanities do in practice.
WHERE IN THE TEXT?
Authors: Doyno Mary Harvey
Published: December 2016

As part of a series of case studies titled “In the Humanities Classroom,” this essay asks how one can teach college students with little or no exposure to close reading, critical analysis, or the premodern world to read a text written c. 202 CE. An instructor at Sacramento State University in California describes her experience introducing students enrolled in a humanities survey course to The Passion of SS. Perpetua and Felicitas—a text that combines the prison diaries of two North African Christians with an eyewitness account of their deaths. In this description of a single, seventy-five-minute class session, the reader is shown how students can be prompted to find the beginnings of a complex interpretation in their own initial, “gut” reactions to an alien and difficult text.
Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex
Authors: Inoue Mayuko , Iwai Ryota , Tabata Hidenori , Konno Daijiro , Komabayashi-Suzuki Mariko , Watanabe Chisato , Iwanari Hiroko , Mochizuki Yasuhiro , Hamakubo Takao , Matsuzaki Fumio , Nagata Koh-ichi , Mizutani Ken-ichi
Published: December 2016

The precise control of neuronal migration and morphological changes during differentiation is essential for neocortical development. We hypothesized that the transition of progenitors through progressive stages of differentiation involves dynamic changes in levels of mitochondrial reactive oxygen species (mtROS), depending on cell requirements. We found that progenitors had higher levels of mtROS, but that these levels were significantly decreased with differentiation. The Prdm16 gene was identified as a candidate modulator of mtROS using microarray analysis, and was specifically expressed by progenitors in the ventricular zone. However, Prdm16 expression declined during the transition into NeuroD1-positive multipolar cells. Subsequently, repression of Prdm16 expression by NeuroD1 on the periphery of ventricular zone was crucial for appropriate progression of the multipolar phase and was required for normal cellular development. Furthermore, time-lapse imaging experiments revealed abnormal migration and morphological changes in Prdm16-overexpressing and -knockdown cells. Reporter assays and mtROS determinations demonstrated that PGC1α is a major downstream effector of Prdm16 and NeuroD1, and is required for regulation of the multipolar phase and characteristic modes of migration. Taken together, these data suggest that Prdm16 plays an important role in dynamic cellular redox changes in developing neocortex during neural differentiation.
TAEL: A zebrafish-optimized optogenetic gene expression system with fine spatial and temporal control
Authors: Reade Anna , Motta-Mena Laura B. , Gardner Kevin H. , Stainier Didier Y. , Weiner Orion D. , Woo Stephanie
Published: December 2016

Here we describe an optogenetic gene expression system optimized for use in zebrafish. This system overcomes the limitations of current inducible expression systems by enabling robust spatial and temporal regulation of gene expression in living organisms. Because existing optogenetic systems show toxicity in zebrafish, we re-engineered the blue-light activated EL222 system, renamed TAEL, for minimal toxicity while exhibiting a large range of induction, fine spatial precision, and rapid kinetics. We validate several strategies to spatially restrict illumination and thus gene induction with the TAEL system. As a functional example, we show that TAEL is able to induce ectopic endodermal cells in the presumptive ectoderm via targeted sox32 induction. We also demonstrate that TAEL can be used to resolve multiple roles of Nodal signaling at different stages of embryonic development. Finally, we show how inducible gene editing can be achieved by combining the TAEL and CRISPR/Cas9 systems. This toolkit should be a broadly useful resource for the fish community.
A vertebrate specific and essential role for sp7/osterix in osteogenesis revealed by gene knock-out in the teleost medaka
Authors: Yu Tingsheng , Graf Martin , Renn Joerg , Schartl Manfred , Larionova Daria , Huysseune Ann , Witten Paul Eckhard , Winkler Christoph
Published: December 2016

Sp7/osterix (osx) encodes a zinc-finger transcription factor that controls osteoblast differentiation in mammals. Although identified in all vertebrate lineages, its role in non-mammalian bone formation remains elusive. Here we show that an osx mutation in medaka results in severe bone defects and larval lethality. Pre-osteoblasts fail to differentiate leading to severe intramembranous and perichondral ossification defects. The notochord sheath mineralizes normally supporting the idea of an osteoblast-independent mechanism for teleost vertebral centra formation. This study establishes a key role for Sp7/Osx for bone formation also in a non-mammalian species, and reveals conserved and non-conserved features in vertebrate bone formation.
An Epha4/Sipa1l3/Wnt pathway regulates eye development and lens maturation
Authors: Rothe Melanie , Kanwal Noreen , Dietmann Petra , Seigfried Franziska , Hempel Annemarie , Schütz Desiree , Reim Dominik , Engels Rebecca , Linnemann Alexander , Schmeisser Michael J. , Bockmann Juergen , Kühl Michael , Boeckers Tobias M. , Kühl Susanne J.
Published: December 2016

The signal-induced proliferation associated family of proteins comprises four members, SIPA1 and SIPA1L1-1L3. Mutations of the human SIPA1L3 gene result in congenital cataracts. In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects. We found a direct interaction between Sipa1l3 and Epha4, building a functional platform for proper ocular development. Epha4 deficiency phenocopied loss of Sipa1l3 and rescue experiments demonstrated that Epha4 acts up-stream of Sipa1l3 during eye development. Both, Sipa1l3 and Epha4 are required for early eye specification. The ocular phenotype, upon loss of either Epha4 or Sipa1l3, was partially mediated by rax. We demonstrated that canonical Wnt signaling is inhibited downstream of Epha4/Sipa1l3 during normal eye development. Depletion of either Sipa1l3 or Epha4 resulted in an up-regulation of axin2 expression, a direct Wnt/β-catenin target gene. In line with this, Sipa1l3 or Epha4 depletion could be rescued by blocking Wnt/β-catenin or activating non-canonical Wnt signaling. We therefore conclude that this pathomechanism prevents proper eye development and maturation of lens fiber cells resulting in congenital cataracts.
Renal disease pathophysiology and treatment: contributions from the rat
Authors: Mullins Linda J. , Conway Bryan R. , Menzies Robert I. , Denby Laura , Mullins John J.
Published: December 2016

The rat has classically been the species of choice for pharmacological studies and disease modeling, providing a source of high-quality physiological data on cardiovascular and renal pathophysiology over many decades. Recent developments in genome engineering now allow us to capitalize on the wealth of knowledge acquired over the last century. Here, we review rat models of hypertension, diabetic nephropathy, and acute and chronic kidney disease. These models have made important contributions to our understanding of renal diseases and have revealed key genes, such as Ace and P2rx7, involved in renal pathogenic processes. By targeting these genes of interest, researchers are gaining a better understanding of the etiology of renal pathologies, with the promised potential of slowing disease progression or even reversing the damage caused. Some, but not all, of these target genes have proved to be of clinical relevance. However, it is now possible to generate more sophisticated and appropriate disease models in the rat, which can recapitulate key aspects of human renal pathology. These advances will ultimately be used to identify new treatments and therapeutic targets of much greater clinical relevance.
Microglia activation in a pediatric rabbit model of tuberculous meningitis
Authors: Tucker Elizabeth W. , Pokkali Supriya , Zhang Zhi , DeMarco Vincent P. , Klunk Mariah , Smith Elizabeth S. , Ordonez Alvaro A. , Penet Marie-France , Bhujwalla Zaver , Jain Sanjay K. , Kannan Sujatha
Published: December 2016

Central nervous system (CNS) tuberculosis (TB) is the most severe form of extra-pulmonary TB and disproportionately affects young children where the developing brain has a unique host response. New Zealand white rabbits were infected with Mycobacterium tuberculosis via subarachnoid inoculation at postnatal day 4-8 and evaluated until 4-6 weeks post-infection. Control and infected rabbit kits were assessed for the development of neurological deficits, bacterial burden, and postmortem microbiologic and pathologic changes. The presence of meningitis and tuberculomas was demonstrated histologically and by in vivo magnetic resonance imaging (MRI). The extent of microglial activation was quantified by in vitro immunohistochemistry as well as non-invasive in vivo imaging of activated microglia/macrophages with positron emission tomography (PET). Subarachnoid infection induced characteristic leptomeningeal and perivascular inflammation and TB lesions with central necrosis, a cellular rim and numerous bacilli on pathologic examination. Meningeal and rim enhancement was visible on MRI. An intense microglial activation was noted in M. tuberculosis-infected animals in the white matter and around the TB lesions, as evidenced by a significant increase in uptake of the tracer 124I-DPA-713, which is specific for activated microglia/macrophages, and confirmed by quantification of Iba-1 immunohistochemistry. Neurobehavioral analyses demonstrated signs similar to those noted in children with delayed maturation and development of neurological deficits resulting in significantly worse composite behavior scores in M. tuberculosis-infected animals. We have established a rabbit model that mimics features of TB meningitis in young children. This model could provide a platform for evaluating novel therapies, including host-directed therapies, against TB meningitis relevant to a young child's developing brain.
Rab2a and Rab27a cooperatively regulate the transition from granule maturation to exocytosis through the dual effector Noc2
Authors: Matsunaga Kohichi , Taoka Masato , Isobe Toshiaki , Izumi Tetsuro
Published: December 2016

Exocytosis of secretory granules entails budding from the trans-Golgi network, sorting and maturation of cargo proteins, and trafficking and fusion to the plasma membrane. Rab27a regulates the late steps in this process, such as granule recruitment to the fusion site, whereas Rab2a functions in the early steps, such as granule biogenesis and maturation. Here, we demonstrate that these two small GTPases simultaneously bind to Noc2 (also known as RPH3AL) in a GTP-dependent manner, although Rab2a binds only after Rab27a has bound. In pancreatic β-cells, the ternary Rab2a–Noc2–Rab27a complex specifically localizes on perinuclear immature granules, whereas the binary Noc2–Rab27a complex localizes on peripheral mature granules. In contrast to the wild type, Noc2 mutants defective in binding to Rab2a or Rab27a fail to promote glucose-stimulated insulin secretion. Although knockdown of any component of the ternary complex markedly inhibits insulin secretion, only knockdown of Rab2a or Noc2, and not that of Rab27a, impairs cargo processing from proinsulin to insulin. These results suggest that the dual effector, Noc2, regulates the transition from Rab2a-mediated granule biogenesis to Rab27a-mediated granule exocytosis.
Effects of activation on the elastic properties of intact soleus muscles with a deletion in titin
Authors: Monroy Jenna A. , Powers Krysta L. , Pace Cinnamon M. , Uyeno Theodore , Nishikawa Kiisa C.
Published: December 2016

Titin has long been known to contribute to muscle passive tension. Recently, it was also demonstrated that titin-based stiffness increases upon Ca2+-activation of wildtype mouse psoas myofibrils stretched beyond overlap of the thick and thin filaments. In addition, this increase in titin-based stiffness upon activation was impaired in single psoas myofibrils from mdm mice with a deletion in titin. Here, we investigate the effects of muscle activation on elastic properties of intact soleus muscles from wildtype and mdm mice to determine whether titin may contribute to active muscle stiffness. Using load-clamp experiments, we compared the stress-strain relationships of elastic elements in active and passive muscles during unloading, and quantified the change in stiffness upon activation. We used the mdm mutation, characterized by a deletion in the N2A region of the Ttn gene, to test the hypothesis that titin contributes to active muscle stiffness. Results show that the elastic modulus of wildtype muscles increases upon activation. Elastic elements began to develop force at lengths that were 15% shorter in active than in passive soleus, and there was a 2.9-fold increase in the slope of the stress - strain relationship. In contrast, mdm soleus showed no effect of activation on the slope or intercept of the stress - strain relationship. These results from intact soleus muscles are qualitatively and quantitatively similar to results from single wildtype psoas myofibrils stretched beyond overlap of the thick and thin filaments. Therefore, it is likely that titin plays a role in the increase of stiffness during rapid unloading that we observed in intact soleus muscles upon activation. The results from intact mdm soleus muscles are also consistent with impaired titin activation observed in single mdm psoas myofibrils stretched beyond filament overlap, further suggesting that the mechanism of titin activation is impaired in skeletal muscles from mdm mice. These results are consistent with the idea that, in addition to the thin filaments, titin is activated upon Ca2+-influx in skeletal muscle.
Thermal sensitivity of motor control of muscle-powered versus elastically powered tongue projection in salamanders
Authors: Scales Jeffrey A. , O'Donnell Mary Kate , Deban Stephen M.
Published: December 2016

Elastic-recoil mechanisms can improve organismal performance and circumvent the thermal limitations of muscle contraction, yet they require the appropriate motor control to operate. We compare muscle activity during tongue projection in salamanders with elastically powered, ballistic projection to those with muscle-powered, non-ballistic projection across a range of temperatures to understand how motor control is integrated with elastically powered movements, and how this integration contributes to reduced thermal sensitivity. Species with ballistic tongue projection activated and deactivated their projector muscles significantly earlier than non-ballistic species, in a pattern consistent with a mechanism in which the muscle strains elastic tissue that subsequently recoils to power projection. Tongue projection was more thermally robust in ballistic species, but in both ballistic and non-ballistic species the projector muscles were activated earlier and for longer as temperature decreased. The retractor muscles showed a similar pattern as the projector muscles, but declined in a similar manner in the two groups. Muscle activity intensity also decreased at low temperatures in both groups, revealing that compensatory muscle activation does not account for the improved thermal robustness in ballistic species. Thus, relatively minor shifts in motor patterns accompanying morphological changes such as increased elastic tissue are sufficient to improve performance and decrease its thermal sensitivity without specialization of muscle contractile physiology.
Photoperiod but not food restriction modulates innate immunity in an opportunistic breeder,Loxia curvirostra
Authors: Schultz Elizabeth M. , Hahn Thomas P. , Klasing Kirk C.
Published: December 2016

An organism's investment in immune function often varies seasonally but understanding of how fluctuations in environmental conditions directly modulate investment remains limited. This experiment investigated how changes in photoperiod and food availability affect investment in constitutive innate immunity and the acute phase response induced by lipopolysaccharide (LPS) injections in captive red crossbills (Loxia curvirostra). Crossbills are reproductively flexible songbirds that specialize on an unpredictably available food resource and display temporal variation in immunity in the wild. Birds were separated into four treatments and exposed to long or short day lengths for six weeks before continuing on an ad-libitum diet or experiencing a 20% food reduction for 10 days. Birds were un-injected or injected with LPS both before and after diet change. Innate immunity was quantified throughout the experiment to assess effects of photoperiod, food availability, and their interactions on hemolysis-hemagglutination, haptoglobin, bacterial killing ability, and leukocyte counts. Overall, increasing day length significantly increased both bacterial killing ability and leukocyte counts. Surprisingly, food restriction had little effect on the immune parameters, potentially owing to the “low cost” environment of captivity and suggesting that investment in innate immunity is prioritized and maintained whenever possible. LPS injections induced stereotypical sickness behaviors and increased bacterial killing ability in short day birds and complement activity (hemolysis) both before and after food restriction. These results demonstrate robust seasonal modulation of immune investment and an ability to maintain innate immunity in the face of limited resources in these temporally flexible songbirds.