bluuebunny/crossref_metadata_2025 huggingface dataset:
Why does Daphne pseudomezereum drop its leaves in the summer? An adaptive alternative to surviving forest shade
Authors: Lei Thomas , Yamashita Naoko , Watanabe Takuya , Kawahara Takayuki , Miyaura Tomiyasu
Published: April 2019

Daphne pseudomezereum A. Gray (Dpm) appears to be the only woody species in the north temperate forest that sheds its leaves in the summer while remaining green over winter (i.e. wintergreen leaf habit). Yet, the reason for this odd leaf habit has not been explored. To this end, we examined the microclimatic settings and ecophysiological traits of Dpm and its three native congeners in a field study of eight natural populations. In addition, we conducted a common garden experiment using Dpm plants where potential carbon gain across the seasons was estimated, using actual field microclimate data. Together, these data tested the hypothesis that Dpm retained traits of an open‐grown upland ancestor, unable to adapt to the deep summer shade, it survived by becoming summer dormant and wintergreen. Our hypothesis was supported by patterns of leaf ecophysiological traits and carbon gain simulations in Dpm, consistent with the energetic feasibility of a summer dormancy followed by an autumn leaf sprout. We also conclude that carbon deficit driven by low light and high respiration cost is the trigger for the leaf habit of Dpm and assert that its phenological strategy represents a rare but viable alternative strategy for persistence in the temperate understory.
Antibiotic locks for the treatment of catheter‐related blood stream infection: Still more hope than data
Authors: Labriola Laura
Published: April 2019

Antibiotic lock therapy (ALT), in conjunction with systemic antibiotics, is recommended by scientific societies as a treatment of uncomplicated catheter‐related bloodstream infections (CRBSI) in hemodynamically stable hemodialysis patients for whom catheter salvage is the goal. The rationale for this strategy is the eradication of intraluminal biofilms by the highly concentrated antibiotic used in the lock. However, the available evidence supporting this recommendation is scanty, and only includes small, short‐term, observational studies (most of them single‐arm), with different definitions of CRBSI cure and variable follow‐up periods. Furthermore, the ability of an antibiotic to eradicate a biofilm is not predicted by its inherent spectrum of antibacterial activity, since sessile microorganisms in their biofilm display other mechanisms of resistance to antibiotics than their planktonic counter‐parts. Additionally, penetration of some antibiotics frequently used into biofilms produced by common microorganisms appears to be low. In this editorial we provide a critical view on the available evidence regarding the efficacy of ALT on the treatment of CRBSI in hemodialysis patients, as well as the microbiological issues and technical challenges of this strategy.
Economic and Social Impacts on Well‐Being: A Cross‐National Multilevel Analysis of Determinants of Access to Water and Sanitation
Authors: Hargrove Andrew
Published: April 2019

Development research identifies water and sanitation access as vital indicators of well‐being. Despite recent improvements, billions still lack access. Case studies and cross‐national research reveal that economic and social processes are associated with water and sanitation access. However, prior research does not control for factors associated with access at multiple levels of analysis. This analysis uses hierarchical generalized linear models for 640,506 households nested within 49 nations to fill this gap. The findings suggest that household wealth and education have robust effects on water and sanitation access, while national characteristics have smaller effects. Furthermore, intraclass correlation coefficients demonstrate that cross‐national analyses miss up to 78 percent of variation by not accounting for subnational variation. While the results highlight the importance of subnational factors, cross‐level interactions between household wealth and education and national characteristics reveal how household wealth and education affect access differently depending on national context. This study synthesizes theories of economic growth and societal capabilities at multiple levels of analysis for understanding water and sanitation access within and between countries.
Endothelial cell barriers: Transport of molecules between blood and tissues
Authors: Yazdani Samaneh , Jaldin‐Fincati Javier R. , Pereira Rafaela V. S. , Klip Amira
Published: April 2019

An endothelial cell monolayer separates interstitia from blood and lymph, and determines the bidirectional transfer of solutes and macromolecules across these biological spaces. We review advances in transport modalities across these endothelial barriers. Glucose is a major fuel for the brain and peripheral tissues, and insulin acts on both central and peripheral tissues to promote whole‐body metabolic signalling and anabolic activity. Blood‐brain barrier endothelial cells display stringent tight junctions and lack pinocytic activity. Delivery of blood glucose and insulin to the brain occurs through their respective carrier (Glucose transporter 1) and receptor (insulin receptor), enacting bona fide transcytosis. At supraphysiological concentrations, insulin is also likely transferred by fluid phase cellular uptake and paracellular transport, especially in peripheral microvascular endothelia. The lymphatic microvasculature also transports insulin but in this case from tissues to lymph and therefrom to blood. This serves to end the hormone's action and to absorb highly concentrated subcutaneously injected insulin in diabetic individuals. The former function may involve receptor‐mediated transcytosis into lymphatic endothelial cells, the latter fluid phase uptake and paracellular transport. Lymphatic capillaries also mediate carrier‐dependent transport of other nutrients and macromolecules. These findings challenge the notion that lymphatic capillaries only transport macromolecules through intercellular flaps.
The R249Q hypertrophic cardiomyopathy myosin mutation decreases contractility in Drosophila by impeding force production
Authors: Bell Kaylyn M. , Kronert William A. , Huang Alice , Bernstein Sanford I. , Swank Douglas M.
Published: April 2019

Key points

Hypertrophic cardiomyopathy (HCM) is a genetic disease that causes thickening of the heart's ventricular walls and is a leading cause of sudden cardiac death.

HCM is caused by missense mutations in muscle proteins including myosin, but how these mutations alter muscle mechanical performance in largely unknown.

We investigated the disease mechanism for HCM myosin mutation R249Q by expressing it in the indirect flight muscle of Drosophila melanogaster and measuring alterations to muscle and flight performance.

Muscle mechanical analysis revealed R249Q decreased muscle power production due to slower muscle kinetics and decreased force production; force production was reduced because fewer mutant myosin cross‐bridges were bound simultaneously to actin.

This work does not support the commonly proposed hypothesis that myosin HCM mutations increase muscle contractility, or causes a gain in function; instead, it suggests that for some myosin HCM mutations, hypertrophy is a compensation for decreased contractility.

Hypertrophic cardiomyopathy (HCM) is an inherited disease that causes thickening of the heart's ventricular walls. A generally accepted hypothesis for this phenotype is that myosin heavy chain HCM mutations increase muscle contractility. To test this hypothesis, we expressed an HCM myosin mutation, R249Q, in Drosophila indirect flight muscle (IFM) and assessed myofibril structure, skinned fibre mechanical properties, and flight ability. Mechanics experiments were performed on fibres dissected from 2‐h‐old adult flies, prior to degradation of IFM myofilament structure, which started at 2 days old and increased with age. Homozygous and heterozygous R249Q fibres showed decreased maximum power generation by 67% and 44%, respectively. Decreases in force and work and slower overall muscle kinetics caused homozygous fibres to produce less power. While heterozygous fibres showed no overall slowing of muscle kinetics, active force and work production dropped by 68% and 47%, respectively, which hindered power production. The muscle apparent rate constant 2πb decreased 33% for homozygous but increased for heterozygous fibres. The apparent rate constant 2πc was greater for homozygous fibres. This indicates that R249Q myosin is slowing attachment while speeding up detachment from actin, resulting in less time bound. Decreased IFM power output caused 43% and 33% decreases in Drosophila flight ability and 19% and 6% drops in wing beat frequency for homozygous and heterozygous flies, respectively. Overall, our results do not support the increased contractility hypothesis. Instead, our results suggest the ventricular hypertrophy for human R249Q mutation is a compensatory response to decreases in heart muscle power output.
Quantitative Measurement of Functional Groups on Nanocarbon Allotropes Surface by Boehm Titration
Authors: Hernández-Ortiz M. , Lozano-López J. D. , Durón S. M. , Galván-Valencia M. , Estevez-Martínez Y. , Durán-Muñoz H. A. , Carrera-Escobedo J. , Guirette-Barbosa O. , Ortiz-Medina I. , Ramírez-Hernández L. A. , Castaño-Meneses V. M.
Published: April 2019

Various nanocarbons (NCs) were used to study their surface groups under standardized Bohem titration, including: multiwalled carbon nanotube (CNT), graphene (G), Vulcan carbon (VC), and nanodiamond (ND). Endpoint-measured titration using second derivative method to quantify carboxylic, lactonic, and phenolic groups created on treated carbon surfaces shows a high precision comparable to other recent reports and with errors of 1 order of magnitude lower. The results exhibit major concentration of carboxyl group increased after the NCs were oxidized compared to the amount of other functional groups like phenols and lactonic groups. It is important highlight, the concentration ratio of carboxyl group with VC:VC-O was showed at 1:77, exhibited a major result regarding other NCs which exhibited ratios of 1:4.5, 1:1.4, and 1:2.5 for ND:ND-O, CNT:CNT-O, and G:G-O, respectively. It is concluded that VC is a NC that competes and excels in its capacity of oxidation with respect to the popular NCs as CNT, graphene (G), and ND.
Optics-less focusing of XUV high-order harmonics
Authors: Quintard L. , Strelkov V. , Vabek J. , Hort O. , Dubrouil A. , Descamps D. , Burgy F. , Péjot C. , Mével E. , Catoire F. , Constant E.
Published: April 2019

Controlling generation of XUV high-order harmonic beams provides focusing of attosecond pulses without any XUV optics.
High-frequency cavity optomechanics using bulk acoustic phonons
Authors: Kharel Prashanta , Harris Glen I. , Kittlaus Eric A. , Renninger William H. , Otterstrom Nils T. , Harris Jack G. E. , Rakich Peter T.
Published: April 2019

Researchers demonstrate optical control of macroscopic, high-frequency acoustic waves for classical and quantum applications.
Location, location, location: Tissue resident memory T cells in mice and humans
Authors: Szabo Peter A. , Miron Michelle , Farber Donna L.
Published: April 2019

This review summarizes key studies that have shaped our understanding of tissue resident memory T cells in mice and humans.
How C-terminal additions to insulin B-chain fragments create superagonists for T cells in mouse and human type 1 diabetes
Authors: Wang Yang , Sosinowski Tomasz , Novikov Andrey , Crawford Frances , White Janice , Jin Niyun , Liu Zikou , Zou Jinhao , Neau David , Davidson Howard W. , Nakayama Maki , Kwok William W. , Gapin Laurent , Marrack Philippa , Kappler John W. , Dai Shaodong
Published: April 2019

In type 1 diabetes, mouse and human CD4
+
T cells recognize mutated and chimeric superagonist insulin B-chain epitopes similarly.
Functioning of Mycobacterial Heat Shock Repressors Requires the Master Virulence Regulator PhoP
Authors: Sevalkar Ritesh Rajesh , Arora Divya , Singh Prabhat Ranjan , Singh Ranjeet , Nandicoori Vinay K. , Karthikeyan Subramanian , Sarkar Dibyendu
Published: April 2019

The regulation of heat shock proteins which protect
M. tuberculosis
against stress generated by macrophages during infection is poorly understood. In this study, we show that PhoP, a virulence regulator of the tubercle bacilli, controls heat shock-responsive genes, an essential pathogenic determinant of
M. tuberculosis
. Our results unravel that in addition to classical DNA-protein interactions, complex mechanisms of regulation of heat shock-responsive genes occur through multiple protein-protein interactions. Together, these findings delineate a fundamental regulatory pathway where transcription factors PhoP, HspR, and HrcA interact with each other to control stress-specific expression of heat shock proteins.
Human Papillomavirus 11 Early Protein E6 Activates Autophagy by Repressing AKT/mTOR and Erk/mTOR
Authors: Zhang Boya , Song Yinjing , Sun Siyuan , Han Rui , Hua Chunting , van der Veen Stijn , Cheng Hao
Published: April 2019

We transfected an HPV11 E6 plasmid into HaCaT cells, H8 cells, and NHEK cells and established a stable cell line expressing the HPV11 E6 protein. Then, we confirmed that HPV11 E6 induces autophagy by suppressing the AKT/mTOR and Erk/mTOR pathways. In contrast to the high-risk HPV E6 genes, HPV11 E6 did not affect the expression of p53. To the best of our knowledge, this study represents the first direct in-depth investigation of the relationship between the LR-HPV E6 gene and autophagy, which may help to reveal the pathogenesis of LR-HPV infection.
Limy bile syndrome presenting as acute acalculous cholecystitis
Authors: Mohammed Ayad Ahmad , Arif Sardar Hassan
Published: April 2019

A 35-year-old woman presented to the surgical clinic complaining of right hypochondrial pain for 4 days. Abdominal examination revealed tenderness on deep palpation in the right hypochonrdium, with no palpable organs or masses. The patient had repeated attacks of the same pain that mandated repeated admissions to the emergency hospital and treated conservatively. The white blood cell count was 13 000 cells/μL. Ultrasound examination of the abdomen showed thick-walled gall bladder, thick bile, with no visible stones and acalculous cholecystitis was the diagnosis. Decision done for laparoscopic cholecystectomy. After removal of the gall bladder and opening the bladder, a thick milky contents was found to fill the gall bladder with no stones. The diagnosis of limy bile syndrome then done. Histopathological examination of the gall bladder showed features of chronic cholecystitis with no malignancy. The patient discharged on the third postoperative day with no complications.
Dealing with pelvic fractures in cats
Authors: Grierson James
Published: April 2019

Pelvic fractures are common in cats and so veterinary surgeons will often be faced with having to manage this type of fracture. Historically, there has been a tendency to say that cats do fine if you just put them on cage rest for six weeks; however, this is outdated and old fashioned advice. There is no doubt that surgery gives a more predictable, comfortable outcome, and a quicker return to function for cats than would be seen with conservative management. This article provides a guide to the decision‐making process around pelvic fractures in cats and the available options for fixation.
Small animal oncology: how to give a client a more accurate prognosis
Authors: Murphy Sue
Published: April 2019

Giving an accurate prognosis is important for many diseases and is a part of everyday veterinary practice. It is especially important with a diagnosis of cancer, not least because many of the treatment modalities are expensive, time consuming and have the potential to cause side effects. Equally, clients often have an experience of cancer treatment and outcomes for themselves or friends and relatives, and they assume that the prognosis for one type of cancer in the human population mirrors what happens to their companion animal. There are many factors that influence an individual animal's prognosis and it is important that veterinary surgeons appreciate the usefulness of these factors to help guide the client's expectations. This article describes how to interpret information obtained regarding the tumours’ histopathological type, grade, stage, and likely response to an appropriate treatment, to provide a prognosis that is as accurate as possible to the client.
Platelet-rich clots as identified by Martius Scarlet Blue staining are isodense on NCCT
Authors: Fitzgerald Sean T , Wang Shunli , Dai Daying , Douglas Andrew , Kadirvel Ramanathan , Gounis Matthew J , Chueh Juyu , Puri Ajit S , Layton Kennith F , Thacker Ike C , Hanel Ricardo A , Sauvageau Eric , Aghaebrahim Amin , Almekhlafi Mohammed A , Demchuk Andrew M , Nogueira Raul G , Pereira Vitor M , Kvamme Peter , Kayan Yasha , Delgado Almandoz Josser E , Yoo Albert J , Kallmes David F , Doyle Karen M , Brinjikji Waleed
Published: April 2019

Background

Current studies on clot characterization in acute ischemic stroke focus on fibrin and red blood cell composition. Few studies have examined platelet composition in acute ischemic stroke clots. We characterize clot composition using the Martius Scarlet Blue stain and assess associations between platelet density and CT density.

Materials and method

Histopathological analysis of the clots collected as part of the multi-institutional STRIP registry was performed using Martius Scarlet Blue stain and the composition of the clots was quantified using Orbit Image Analysis (www.orbit.bio) machine learning software. Prior to endovascular treatment, each patient underwent non-contrast CT (NCCT) and the CT density of each clot was measured. Correlations between clot components and clinical information were assessed using the χ2test.

Results

Eighty-five patients were included in the study. The mean platelet density of the clots was 15.7% (2.5–72.5%). There was a significant correlation between platelet-rich clots and the absence of hyperdensity on NCCT, (ρ=0.321, p=0.003*, n=85). Similarly, there was a significant inverse correlation between the percentage of platelets and the mean Hounsfield Units on NCCT (ρ=−0.243, p=0.025*, n=85).

Conclusion

Martius Scarlet Blue stain can identify patients who have platelet-rich clots. Platelet-rich clots are isodense on NCCT.
Top dietary sources of energy, sodium, sugars, and saturated fats among Canadians: insights from the 2015 Canadian Community Health Survey
Authors: Kirkpatrick Sharon I. , Raffoul Amanda , Lee Kirsten M. , Jones Amanda C.
Published: April 2019

Dietary factors are major contributors to morbidity and mortality, and significant attention is being paid to interventions to support healthy eating, including through the creation of a healthier food supply. The objective of this study was to inform interventions to support healthy eating by examining the top dietary sources of calories, sodium, sugars, and saturated fats among Canadians in relation to sex, age, and income. We drew upon data from the 2015 Canadian Community Health Survey, which collected interviewer-administered 24-h dietary recalls from Canadians who were 1 year of age and older (n = 20 176), residing in the 10 provinces. Foods and beverages were grouped into 91 mutually exclusive categories (e.g., 100% fruit juice, fruit drinks). On the basis of the average proportion contributed, the top 20 sources of each dietary component were identified for all individuals and by sex–age and income groups. The mean amount of each dietary component contributed by each category (per capita and per consumer) and the proportions of persons consuming items in each category were also examined. Top sources included commonly consumed items (e.g., breads and flatbreads as sources of sodium), as well as those high in a given dietary component (e.g., soda as a source of sugars). Several food and beverage categories were top contributors to more than one dietary component examined, suggesting possible priorities for intervention and future analyses. The identification of major sources of calories and nutrients of concern can inform population health efforts, such as reformulation, to improve the health of Canadians.
β-Adrenoreceptors do not oppose sympathetic vasoconstriction in resting and contracting skeletal muscle of male rats
Authors: Cooper Ian R. , Just Timothy P. , DeLorey Darren S.
Published: April 2019

Sympathetic nervous system (SNS) vasoconstriction is primarily achieved through the binding of norepinephrine (NE) to α-adrenoreceptors. However, NE may also bind to β-adrenoreceptors and cause vasodilation that may oppose/blunt SNS-mediated vasoconstriction. Therefore, this study investigated the hypothesis that β-adrenoreceptor–mediated vasodilation opposes evoked vasoconstriction in resting and contracting skeletal muscle. Male (n = 9) Sprague–Dawley rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain and measurement of arterial blood pressure and femoral artery blood flow. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae skeletal muscle contraction before (control) and after β-adrenoreceptor blockade (propranolol; 0.075 mg·kg−1, intravenously). β-Adrenoreceptor blockade did not alter (P > 0.05) baseline hemodynamics or the hyperemic response to exercise. At the 2 Hz stimulation frequency, sympathetic vasoconstriction was similar (P > 0.05) in control and β-blockade conditions in resting (control, −34% ± 6%; β-blockade, −33% ± 8%) and contracting (control, −16% ± 6%; β-blockade, −14% ± 7%) muscle. At the 5 Hz stimulation frequency, sympathetic vasoconstrictor responsiveness was reduced (main effect of drug, P < 0.05) following β-blockade (rest: control, −52% ± 7%; β-blockade, −51% ± 9%; contraction: control, −32% ± 11%; β-blockade, −29% ± 13%).

Novelty These data indicate that β-adrenoreceptor blockade did not augment sympathetic vasoconstriction at rest or during exercise. The study demonstrates that β-adrenoreceptors do not oppose evoked sympathetic vasoconstriction in resting or contracting skeletal muscle or contribute to functional sympatholysis.
FINANCIAL INCLUSION AND MACROECONOMIC STABILITY IN EMERGING AND FRONTIER MARKETS
Authors: VO ANH THE , VAN LOAN THI-HONG , VO DUC HONG , MCALEER MICHAEL
Published: April 2019

Financial inclusion, being considered as a key enabler to reducing poverty and boosting prosperity in emerging and frontier markets such as Vietnam, is the process in which individuals and small businesses are provided with an access to useful and affordable financial products and services. The extant literature on the empirical evidence regarding the contribution of financial inclusion to macroeconomic stability is mixed. This paper investigates the linkages between financial inclusion and macroeconomic stability, which has not yet been thoroughly examined in the literature, for 22 emerging and frontier economies from 2008 to 2015, with particular focus on a potential optimal level. Using the panel threshold estimation technique, the empirical findings show that financial inclusion, as approximated by the growth rate in the number of bank branches over 100,000 account holders, is found to enhance financial stability under a certain threshold. Financial inclusion is also found to be of benefit to maintaining stable inflation and output growth. Policy implications are also discussed on the basis of the important empirical findings.
THE DETERMINANTS OF FINANCIAL INSTABILITY IN EMERGING COUNTRIES
Authors: VO DUC HONG , NGUYEN VUONG MINH , QUANG-TON LE PHAT , PHAM THACH NGOC
Published: April 2019

Financial integration has greatly contributed to economic growth and development around the globe, in particular for developing countries. However, this process of financial integration has also provided threats in the form of instability which threaten the progress of economic growth and development. The objective of this study is to examine a set of indicators which are valid and indicative of financial instability in the case of developing countries. A panel data of 17 developing countries during the period 2000–2017 is utilized. The credit growth is used as a proxy of financial instability. Standard methods such as the pooled OLS, fixed effect model and random effect model are considered to ensure robustness. Empirical findings from this study indicate that the key determinants of financial instability in developing countries including Vietnam include the GDP growth rate, inflation rate, the growth rate of base money, the change in foreign exchange reserves, lending interest rate, returns in the stock market and the return on equity ratio of the banking sector. Findings from this study appear to support the views of Post-Keynesians in relation to the mechanism leading to financial instability, in particular for developing markets.
Utilization and Protection of Water Resources in China: 1978–2018
Authors: XIA Jun , ZUO Qiting
Published: April 2019

Since the reform and opening up, China has undergone fundamental economic and social changes, along with which the concepts, researches, and practices related to the utilization and protection of water resources have also changed dramatically. Therefore, it is of great significance to systematically summarize China’s 40-year history of water use and protection, and look to the future demand in the new era. By consulting the literature, the authors have sorted out the process of water resources utilization and protection in China between 1978 and 2018, and divided it into development-focused stage (1978–1999), comprehensive utilization stage (2000–2012) and protection-focused stage (2013 to present). Based on the development demand in the new era, the authors believe that the protection-focused stage will continue for a period of time (till 2025 or so), and a smart water use stage will emerge in the years to come. The authors have also proposed the priorities and directions for future research on water resources utilization and protection in the construction of the Belt and Road, the development of the Yangtze River Economic Zone, the coordinated development of Beijing–Tianjin–Hebei region, the construction of the Xiong’ an New Area, and the implementation of the Rural Revitalization Strategy.
Evoking History: The Belt & Road Initiative and Regional Connectivity
Authors: Tseng Chin-Yin
Published: April 2019

As the historical symbol behind China’s 21st century development strategy of the Belt & Road Initiative (BRI), the notion of the Silk Road(s) was never that of one singular passageway, but a network of contacts across the Eurasian continent, over both land and water. For more than two millennia, commerce, conquests, and diplomatic activities took place across this trans-continental network, bringing with them people, commodity, and ideas. In this paper, I will discuss how historical cultural spheres crossed over where the Silk Road(s) linked one group of people to another, promoting regional connectivity and co-prosperity. Using specific objects as case study, the Hoxne pepper pot and Roman glass bowls demonstrate how, as early as the Roman period, the Chinese central kingdom was already in contact with the Roman empire. Material cultural contact and adaptation was never a one-way trend, but always with ramifications to be experienced in the everyday life of all the peoples involved. Since its inception, the Silk Road(s) existed for, and in turn, benefited from, speed and efficacy in the transportation of people and goods. As the era of camels, horses, and sailing ships fades into history, China’s push for the development of high-speed rail emerges to be the most efficient and favored mode of transportation to realize true regional connectivity for BRI to kick into action.
Thermal evolution of the Scandian hinterland, Naver nappe, northern Scotland
Authors: Mako Calvin A. , Law Richard D. , Caddick Mark J. , Ryan Thigpen J. , Ashley Kyle T. , Cottle John , Kylander-Clark Andrew
Published: April 2019

The Northern Highlands Terrane of Scotland hosts several thrust nappes that were deformed and metamorphosed during the Silurian Scandian orogeny. Quantitative petrological analysis of metamorphic assemblages indicates that the hinterland-positioned Naver nappe experienced decompression heating from 8–9 kbar and 600°C to 6–7 kbar and 700°C. Monazite–xenotime thermometry and geochronology delineate a detailed temperature–time history for the Naver nappe. Monazite often exhibits compositional zoning, which is used to establish multiple temperature–time points in several samples. These data indicate that the Naver nappe experienced relatively fast heating (
c.
50°C myr
−1
) and relatively slow cooling (15–20°C myr
−1
), with peak temperatures occurring at
c.
425 Ma. This temperature–time evolution is compatible with the early Emsian (407–403 Ma) deposition of unmetamorphosed conglomerates that rest on high-grade metamorphic rocks in the Naver nappe, but requires an acceleration in the cooling rate to 40–50°C myr
−1
at 420–410 Ma. Geochronological constraints from this study and previous work suggest that deformation and metamorphism in the hinterland of the Scandian orogen in northern mainland Scotland are younger than the
c.
430 Ma deformation in the foreland-positioned Moine thrust zone. We postulate that heat from pervasive granitic intrusions in the Naver nappe weakened the crust, allowing deformation to retreat to the hinterland of the orogen.

Supplementary material:
A description of our analytical methods, all U–Pb-trace element data, additional figures explaining our petrological analysis and other relevant data are available at:
https://doi.org/10.6084/m9.figshare.c.4458041
Knockdown of CD44 expression decreases valve interstitial cell calcification in vitro
Authors: Baugh Lauren , Watson Matthew C. , Kemmerling Erica C. , Hinds Philip W. , Huggins Gordon S. , Black Lauren D.
Published: April 2019

The lack of pharmaceutical targets available to treat patients with calcific aortic valve disease (CAVD) necessitates further research into the specific mechanisms of the disease. The significant changes that occur to the aortic valves extracellular matrix (ECM) during the progression of CAVD suggests that these proteins may play an important role in calcification. Exploring the relationship between valve interstitial cells (VICs) and the ECM may lead to a better understand of CAVD mechanisms and potential pharmaceutical targets. In this study, we look at the effect of two ECM components, collagen and hyaluronic acid (HA), on the mineralization of VICs within the context of a two-dimensional, polyacrylamide (PAAM) model system. Using a novel, nondestructive imaging technique, we were able to track calcific nodule development in culture systems over a 3-wk time frame. We saw a significant increase in the size of the nodules grown on HA PAAM gels as compared with collagen PAAM gels, suggesting that HA has a direct effect on mineralization. Directly looking at the two known receptors of HA, CD44 and receptor for HA-mediated motility (RHAMM), and using siRNA knockdown revealed that a decrease in CD44 expression resulted in a reduction of calcification. A decrease in CD44, through siRNA knockdown, reduces mineralization on HA PAAM gels, suggesting a potential new target for CAVD treatment.

NEW & NOTEWORTHY Our in vitro model of calcific aortic valve disease shows an interaction between the hyaluronic acid binding protein CD44 with the osteogenic factor OPN as a potential mechanism of aortic valve calcification. Using siRNA knockdown of CD44, we show an upregulation of OPN expression with a decrease in overall mineralization.
Central ANG-(1–7) infusion improves blood pressure regulation in antenatal betamethasone-exposed sheep and reveals sex-dependent effects on oxidative stress
Authors: Hendricks Alexa S. , Lawson Matthew J. , Figueroa Jorge P. , Chappell Mark C. , Diz Debra I. , Shaltout Hossam A.
Published: April 2019

Fetal exposure to betamethasone (BMX) as a consequence of glucocorticoid administration to women threatening premature delivery may lead to long-term deleterious effects on the cardiovascular system and dysregulation of blood pressure in exposed adults. Indeed, adult offspring of BMX sheep exhibit increased mean arterial pressure (MAP) and attenuated baroreflex sensitivity (BRS) that are associated with lower medullary and cerebrospinal fluid (CSF) angiotensin-(1–7) [(ANG-(1–7)] content. Thus we determined the effects of ANG-(1–7) supplementation in the CSF on MAP, BRS, blood pressure (BPV) and heart rate variability (HRV) in conscious animals. The peptide or artificial CSF (aCSF) was infused continuously into the lateral ventricle (intracerebroventricular) of 4-mo-old male and female BMX sheep for 2 wk. Analysis of data from males and females combined revealed that intracerebroventricular ANG-(1–7) significantly lowered MAP and heart rate and improved BRS as compared with baseline; intracerebroventricular aCSF did not change these indexes. Similar patterns were observed for altered hemodynamics and autonomic function produced by intracerebroventricular ANG-(1–7) in both sexes. Oxidative stress and MAP kinase (MAPK) activation were lower in tissues from the dorsomedial medulla (DMM) of ANG-(1–7)-treated males but were unchanged in the treated females, when assessed at the end of the treatment period. We conclude that in the face of ANG-(1–7) deficiency in CSF and medullary tissue in BMX sheep intracerebroventricular supplementation of ANG-(1–7) lowers MAP and restores the impaired autonomic function to a similar degree in both males and females; however, the attenuation of MAPK and oxidative stress within the DMM was evident only in males.

NEW & NOTEWORTHY We demonstrate that intracerebroventricular angiotensin-(1–7) [(ANG-(1–7)] treatment for 2 wk in antenatal betamethasone-exposed sheep provides beneficial effects on blood pressure and autonomic function. The physiological improvements are accompanied by an attenuation of oxidative stress in males but not females. The finding that ANG-(1–7) supplementation lowers blood pressure and restores the impaired autonomic function in a model of fetal programming previously shown to exhibit a deficiency in cerebrospinal fluid and brain tissue illustrates the potential for new therapeutic strategies for reducing cardiovascular dysfunction arising from prenatal events.
CYP4A/20-HETE regulates ischemia-induced neovascularization via its actions on endothelial progenitor and preexisting endothelial cells
Authors: Chen Li , Tang Samantha , Zhang Frank F. , Garcia Victor , Falck John R. , Schwartzman Michal L. , Arbab Ali S. , Guo Austin M.
Published: April 2019

20-Hydroxyeicosatetraenoic acid (20-HETE) was recently identified as a novel contributor of ischemia-induced neovascularization based on the key observation that pharmacological interferences of CYP4A/20-HETE decrease ischemic neovascularization. The objective of the present study is to examine whether the underlying cellular mechanisms involve endothelial progenitor cells (EPCs) and preexisting endothelial cells (ECs). We found that ischemia leads to a time-dependent increase of cyp4a12 expression and 20-HETE production, which are endothelial in origin, using immunofluorescent microscopy, Western blot analysis, and LC-MS/MS. This is accompanied by increases in the tissue stromal cell-derived factor-1α (SDF-1α) expressions as well as SDF-1α plasma levels, EPC mobilization from bone marrow, and subsequent homing to ischemic tissues. Pharmacological interferences of CYP4A/20-HETE with a 20-HETE synthesis inhibitor, dibromo-dodecenyl-methylsulfimide (DDMS), or a 20-HETE antagonist, N-(20-hydroxyeicosa-6( Z), 15( Z)-dienoyl) glycine (6, 15-20-HEDGE), significantly attenuated these increases. Importantly, we also determined that 20-HETE plays a novel role in maintaining EPC functions and increasing the expression of Oct4, Sox2, and Nanog, which are indicative of increased progenitor cell stemness. Flow cytometric analysis revealed that pharmacological interferences of CYP4A/20-HETE decrease the EPC population in culture, whereas 20-HETE increases the cultured EPC population. Furthermore, ischemia also markedly increased the proliferation, oxidative stress, and ICAM-1 expression in the preexisting EC in the hindlimb gracilis muscles. We found that these increases were markedly negated by DDMS and 6, 15-20-HEDGE. Taken together, CYP4A/20-HETE regulates ischemia-induced compensatory neovascularization via its combined actions on promoting EPC and local preexisting EC responses that are associated with increased neovascularization.

NEW & NOTEWORTHY CYP4A/20-hydroxyeicosatetraenoic acid (20-HETE) was recently discovered as a novel contributor of ischemia-induced neovascularization. However, the underlying molecular and cellular mechanisms are completely unknown. Here, we show that CYP4A/20-HETE regulates the ischemic neovascularization process via its combined actions on both endothelial progenitor cells (EPCs) and preexisting endothelial cells. Moreover, this is the first study, to the best of our knowledge, that associates CYP4A/20-HETE with EPC differentiation and stemness.
A novel traditional Chinese medicine ameliorates fatigue-induced cardiac hypertrophy and dysfunction via regulation of energy metabolism
Authors: Huang Rong , Cui Yuan-Chen , Wei Xiao-Hong , Pan Chun-Shui , Li Quan , He Shu-Ya , Fan Jing-Yu , Han Jing-Yan
Published: April 2019

Prolonged exercise and exercise training can adversely affect cardiac function in some individuals. QiShenYiQi Pills (QSYQ), which are a compound Chinese medicine, have been previously shown to improve pressure overload-induced cardiac hypertrophy. We hypothesized that QSYQ can ameliorate as well the fatigue-induced cardiac hypertrophy. This study was to test this hypothesis and underlying mechanism with a focus on its role in energy regulation. Male Sprague-Dawley rats were used to establish exercise adaptation and fatigue model on a motorized rodent treadmill. Echocardiographic analysis and heart function test were performed to assess heart systolic function. Food-intake weight/body weight and heart weight/body weight were assessed, and hematoxylin and eosin staining and immunofluorescence staining of myocardium sections were performed. ATP synthase expression and activity and ATP, ADP, and AMP levels were assessed using Western blot and ELISA. Expression of proteins related to energy metabolism and IGF-1R signaling was determined using Western blot. QSYQ attenuated the food-intake weight/body weight decrease, improved myocardial structure and heart function, and restored the expression and distribution of myocardial connexin 43 after fatigue, concomitant with an increased ATP production and a restoration of metabolism-related protein expression. QSYQ upgraded the expression of IGF-1R, P-AMPK/AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, P-phosphatidylinositol 3-kinase (PI3K)/PI3K, and P-Akt/Akt thereby attenuated the dysregulation of IGF-1R signaling after fatigue. QSYQ relieved fatigue-induced cardiac hypertrophy and enhanced heart function, which is correlated with its potential to improve energy metabolism by regulating IGF-1R signaling.

NEW & NOTEWORTHY Prolonged exercise may impact some people leading to pathological cardiac hypertrophy. This study using an animal model of fatigue-induced cardiac hypertrophy provides evidence showing the potential of QiShenYiQi Pills, a novel traditional Chinese medicine, to prevent the cardiac adaptive hypertrophy from development to pathological hypertrophy and demonstrates that this effect is correlated with its capacity for regulating energy metabolism through interacting with insulin-like growth factor-1 receptor.
Different Rates of Chicken Manure and NPK 15-15-15 Enhanced Performance of Sunflower (Helianthus annuusL.) on Ferruginous Soil
Authors: Abumere V. I. , Dada O. A. , Adebayo A. G. , Kutu F. R. , Togun A. O.
Published: April 2019

Utilization of adequate fertilizer rate enhances soil physical and chemical properties, minimizes soil nutrient imbalance, and promotes better crop growth and development. The study investigated the influence of varying rates of chicken manure and NPK fertilizers as it affected growth, nutrient uptake, seed yield, and oil yield of sunflower on nutrient-limiting soil. Field experiments were carried out during 2014 and 2015 planting seasons for both main and residual studies. There were eight treatments comprising four rates of chicken manure (5, 10, 15, and 20 t·ha−1), three rates of NPK (30, 60, and 90 kg·N·ha−1), and control. The experiment was laid out in a randomized complete block design with three replicates. Growth, yield, dry matter and proximate, nutrient uptake concentration, and oil content were determined following standard procedures. Data were analyzed using ANOVA, and means were compared with the Duncan multiple range test (DMRT) atp≤0.05. Performance of sunflower was superior on the field fertilized with 10 t·ha−1chicken manure which was comparable to 90 kg·N·ha−1NPK fertilizer. Sunflower seed yield and oil quality were superior in plots supplied with 10 t·ha−1chicken manure which was comparable to 60 kg·N·ha−1NPK. Growth, yield, dry matter, and proximate content were least in the unfertilized plots.
The Improvedexp⁡-Φξ-Expansion Method and New Exact Solutions of Nonlinear Evolution Equations in Mathematical Physics
Authors: Chen Guiying , Xin Xiangpeng , Liu Hanze
Published: April 2019

Theexp(-Φ(ξ))-expansion method is improved by presenting a new auxiliary ordinary differential equation forΦ(ξ). By using this method, new exact traveling wave solutions of two important nonlinear evolution equations, i.e., the ill-posed Boussinesq equation and the unstable nonlinear Schrödinger equation, are constructed. The obtained solutions contain Jacobi elliptic function solutions which can be degenerated to the hyperbolic function solutions and the trigonometric function solutions. The present method is very concise and effective and can be applied to other types of nonlinear evolution equations.
Targeting the Temporal Dynamics of Hypoxia-Induced Tumor-Secreted Factors Halts Tumor Migration
Authors: Singh Manjulata , Tian Xiao-Jun , Donnenberg Vera S. , Watson Alan M. , Zhang JingYu , Stabile Laura P. , Watkins Simon C. , Xing Jianhua , Sant Shilpa
Published: April 2019

Targeting microenvironmental factors that foster migratory cell phenotypes is a promising strategy for halting tumor migration. However, lack of mechanistic understanding of the emergence of migratory phenotypes impedes pharmaceutical drug development. Using our three-dimensional microtumor model with tight control over tumor size, we recapitulated the tumor size–induced hypoxic microenvironment and emergence of migratory phenotypes in microtumors from epithelial breast cells and patient-derived primary metastatic breast cancer cells, mesothelioma cells, and lung cancer xenograft cells. The microtumor models from various patient-derived tumor cells and patient-derived xenograft cells revealed upregulation of tumor-secreted factors, including matrix metalloproteinase-9 (MMP9), fibronectin (FN), and soluble E-cadherin, consistent with clinically reported elevated levels of FN and MMP9 in patient breast tumors compared with healthy mammary glands. Secreted factors in the conditioned media of large microtumors induced a migratory phenotype in nonhypoxic, nonmigratory small microtumors. Subsequent mathematical analyses identified a two-stage microtumor progression and migration mechanism whereby hypoxia induces a migratory phenotype in the initialization stage, which then becomes self-sustained through a positive feedback loop established among the tumor-secreted factors. Computational and experimental studies showed that inhibition of tumor-secreted factors effectively halts microtumor migration despite tumor-to-tumor variation in migration kinetics, while inhibition of hypoxia is effective only within a time window and is compromised by tumor-to-tumor variation, supporting our notion that hypoxia initiates migratory phenotypes but does not sustain it. In summary, we show that targeting temporal dynamics of evolving microenvironments, especially tumor-secreted factors during tumor progression, can halt tumor migration.

Significance:

This study uses state-of-the-art three-dimensional microtumor models and computational approaches to highlight the temporal dynamics of tumor-secreted microenvironmental factors in inducing tumor migration.
Estrogen Receptor Covalent Antagonists: The Best Is Yet to Come
Authors: Furman Craig , Hao Ming-Hong , Prajapati Sudeep , Reynolds Dominic , Rimkunas Victoria , Zheng Guo Z. , Zhu Ping , Korpal Manav
Published: April 2019

The development of tamoxifen and subsequent estrogen receptor alpha (ERα) antagonists represents a tremendous therapeutic breakthrough in the treatment of breast cancer. Despite the ability of ERα antagonists to increase survival rates, resistance to these therapies is an all-too-common occurrence. The majority of resistant tumors, including those with hotspot mutations in the ligand-binding domain of ERα, remain dependent on ERα signaling, indicating that either a more potent or novel class of antagonist could have clinical benefit. With this thought in mind, we developed a novel ERα antagonist that exhibits enhanced potency due to its ability to covalently target a unique cysteine in ER. This review describes the design of this antagonist, H3B-5942, and discusses opportunities for future improvements, which could reduce the risk of escape mutations to this therapeutic modality.
Words, Silence, Experiences: Derrida’s Unheimlich Responsibility
Authors: Scott Charles E.
Published: April 2019

In its engagement with Derrida’s unheimlich responsibility elaborated in The Beast and the Sovereign, Volume One, this essay is about death, words, silence, and lives of people and animals. It is also about experiences that to varying degrees bring lives to words and words to lives. Its guiding hypotheses are that death, words, silence, and lives in their happenings exceed the laws that function to identify them and that none of their happenings is sovereign in relation to the others. The essay culminates with Derrida’s engagement with ungrounded time when completion and beginning are simultaneous. That simultaneity constitutes a threshold in which people must respond. For Derrida the threshold is shadowed by his own approaching death.
Rhythm and Technics: On Heidegger’s Commentary on Rimbaud
Authors: Hui Yuk
Published: April 2019

This article takes up Heidegger’s commentary on Rimbaud’s Lettres du voyant as the starting point for an exploration of the question of rhythm in Heidegger’s thought, and an attempt to situate it within his understanding of technics and Being. Besides pursuing a historical study of the concept of rhythm in Heidegger’s work, this article proposes to understand rhythm through the concept of individuation. It responds to the French philosopher Jacques Garelli’s critique of Heidegger that the latter ignores the question of individuation and always starts with beings that are already individuated. On the contrary, this article attempts to sketch a theory of individuation of rhythm in Heidegger’s proper thinking through a re-interpretation of the Fug—a word he used to translate the Greek word δίκη and words derived from it: joint (Fuge), structure (Gefüge), submission (sich fugen), etc.
Dwelling and Hospitality: Heidegger and Hölderlin
Authors: Winkler Rafael
Published: April 2019

In this article, I focus on Heidegger’s conception of hospitality in his first and final lectures on Hölderlin’s Germania (1934/5), Remembrance (1941/2), and The Ister (1942). I argue that the hospitality of the foreigner for Heidegger is the condition of possibility of dwelling understood as the happening of history.

In the first section I analyze the notions of hospitality in Levinas and Derrida. The second section unpacks some of the senses of the earth in Heidegger as the site of man’s historical dwelling, whereas in the third section I focus on holy mourning as the disposition that reveals the earth as the uncanny ground of history. In the final section, I spell out Heidegger’s conception of hospitality, the greeting, and the foreign guest.