bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higenamine, a Dual Agonist for β
1- and β
2-Adrenergic Receptors Identified by Screening a Traditional Chinese Medicine Library
Authors: Chen Yanmin , Guo Bujing , Zhang Hongda , Hu Lihong , Wang Jue 
Published: June 2019

AbstractChronic heart failure is the terminal stage of various cardiovascular diseases. Despite the availability of several classes of drugs, there is still an unmet need for effective treatment. Based on bench work during the past two decades, we have proposed that enhancement of β
2-adrenergic receptor signaling in combination with the presently preferred β
1-adrenergic receptor blockade would be a promising strategy. Chinese herbal medicines have been shown to be effective in the treatment of heart failure, although the mechanisms largely remain unknown. In the present study, we screened an herbal medicine compound/extract library for β-adrenergic receptor ligands to determine the target of certain effective botanical remedies and seek a leading compound(s) for chronic heart failure treatment. Using a high-throughput screening assay, we identified higenamine, which has a long history in chronic heart failure treatment in traditional Chinese medicine, to be a potent β-adrenergic receptor agonist. Further experiments using specific inhibitors showed that higenamine activated both β
1-adrenergic receptor and β
2-adrenergic receptor. Inhibition of its action by pertussis toxin (a Gi inhibitor) indicated that it is a β
2-adrenergic receptor Gs/Gi dual agonist. Contractility experiments demonstrated a positive inotropic effect of higenamine. In conclusion, we found an herbal compound, higenamine, to be a dual agonist for β
1/β
2-adrenergic receptors with no preference in stimulating the Gs and Gi pathways in β
2-adrenergic receptor signaling. Our results elucidated not only the target of higenamine to explain its pharmacological effect in treating chronic heart failure, but also the mechanisms of its cardiac toxicity.
New Alkene Cyclopropanation Reactions Enabled by Photoredox Catalysis via Radical Carbenoids
Authors: Herraiz Ana G. , Suero Marcos G. 
Published: June 2019

We describe the recent emergence of a new approach for the synthesis of cyclopropane rings by means of photoredox catalysis. This methodology relies on the photocatalytic generation of radical carbenoids or carbenoid-like radicals as cyclopropanating species, and is characterized by excellent functional group tolerance, chemoselectivity and the ability to form cyclopropanes with excellent control from E/Z alkene mixtures. The mild reaction conditions and employment of user-friendly reagents are highly attractive features that may lead to this approach being used in academic and industrial laboratories.1	Introduction2	Photoredox-Catalyzed Alkene Cyclopropanations with Radical Carbenoids3	Conclusions and Outlook
Infertility Services for Veterans: Policies, Challenges, and Opportunities
Authors: Edmonds Stephanie W. , Zephyrin Laurie C. , Christy Alicia , Ryan Ginny L. 
Published: June 2019

AbstractInfertility prevalence and care needs among male and female Veterans are understudied topics. The Veterans Health Administration (VHA) medical benefits package covers full infertility evaluation and many infertility treatments for Veterans but not, by law, for their spouses. In vitro fertilization (IVF) is also specifically excluded from this medical benefits package by regulation. Congress passed a law in 2016 that allowed VHA to provide IVF to Veterans and their legal spouses, and broader infertility benefits to the legal spouse, if the Veteran has a service-connected condition associated with his or her infertility, with some limitations. As the Veteran population becomes increasingly female, research efforts in reproductive health, including infertility, are expanding and evolving. This includes a nationwide study currently underway examining infertility among male and female Veterans and associations with military-related trauma, such as injury, posttraumatic stress disorder, military sexual trauma, and toxin exposure. In this review, we describe the state of the science and policy on infertility care in the VHA along with challenges and opportunities that exist within the VHA system.
Obstetric Outcomes in U.S. Veterans: Emerging Knowledge, Considerations, and Gaps
Authors: Hugin Michele , Shaw Jonathan G. 
Published: June 2019

AbstractIn the post-9/11 era, the number of young women serving, and deploying, in the military grew rapidly; as they exit service, there is tremendous increase in reproductive-aged women Veterans. Here, we review the limited but growing research regarding Veterans' pregnancy and obstetric outcomes. U.S. women Veterans returning from deployment carry a high burden of physical and mental health conditions, and often trauma. As poor mental health is known to predict poorer maternal and infant sequelae, there are unique concerns around perinatal outcomes in Veterans. Accordingly, there is new attention to their reproductive risks and needs—evidenced by recent research and programmatic efforts within the VA. Emerging research suggests that the unique health profiles of pregnant Veterans, including prevalent posttraumatic stress disorder, predict increased risk of preterm birth, preeclampsia, and gestational diabetes. In the most contemporary large study, relying on California birth data, Veterans who relied on VA for their health care coverage were high risk, with increased rates of preeclampsia and Cesarean delivery. Additionally, Veterans' infants (compared with non-Veterans') were more likely to require NICU care. Additional research is needed to explore upstream factors leading to these poorer outcomes. Current effort to coordinate VA and non-VA care for Veteran mothers is warranted.
Surgical Management of Thoracolumbar Myelopathies in Pug Dogs with Concurrent Articular Facet Dysplasia
Authors: Tauro Anna , Rose Jeremy , Rusbridge Clare , Driver Colin J. 
Published: June 2019

Objectives The aim of this article is to present the outcome of vertebral stabilization using pins and polymethylmethacrylate in isolation or with concurrent spinal cord decompression for thoracolumbar myelopathies in Pug dogs with associated caudal articular process dysplasia.
Materials and Methods Retrospective case review of 14 Pug dogs with thoracolumbar myelopathy and concurrent caudal articular process dysplasia identified with magnetic resonance imaging and computed tomography. Pug dogs were graded based on the Texas Spinal Cord Injury Scale and clinical follow-up was performed immediately after surgery, at the discharge and at during the postoperative period (median 5 months). Postoperative computed tomography was performed immediately post-surgical intervention in all cases and a variable postoperative time (6 weeks or 6 months). Follow-up with telephone interview with owners was performed at a median time of 12 months postoperatively.
Results Median age of presentation was 8.5 years. In 10/14 cases, neurological improvement was observed, while urinary/faecal incontinence resolved in only two of seven affected cases. Other congenital vertebral malformations were identified in 9/14 cases.
Clinical Significance In our population of Pug dogs with thoracolumbar myelopathy and concurrent caudal articular process dysplasia, vertebral stabilization in isolation or with concurrent spinal cord decompression appeared to result in a favourable clinical outcome in the majority of patients. This technique may be favourable for myelopathies with a reportedly poor surgical outcome in this breed.
Avulsion of the Accessory-Carpal Ligaments and Sagittal Fracture of the Ulnar Carpal Bone in a Foal
Authors: Tatarniuk Dane M. , White Robin , Modesto Rolf B. , Miles Kristina G. 
Published: June 2019

AbstractA 45-day-old foal presented for weight bearing lameness. Radiography revealed an abnormal radiolucent line associated with the proximal ulnar carpal bone and a separate curvilinear mineral opacity palmaromedial to the distal radial epiphysis. Computed tomography illustrated a sagittal, biarticular, non-displaced fracture of the ulnar carpal bone with small separate fragments associated with the accessory-ulnar and accessory-radial carpal ligaments. The foal was treated conservatively with rest and adjunct intra-articular hyaluronic acid. The lameness resolved within 90 days. Full range of motion of the carpus returned within 120 days following an active rehabilitation protocol. This report details avulsion of the accessory-carpal ligaments and sagittal fracture of the ulnar carpal bone secondary to presumed hyperextension injury.
What principle of difference for a truly egalitarian social democracy? Rereading Rawls after social democracy’s failures
Authors: Barata André , Cabrita Maria João 
Published: June 2019

AbstractSocial democracy based on welfare and the redistribution of social contributions is failing. The accumulation of wealth and the increase in inequalities are the two faces of Janus that social democracy has not been able to contain over the recent decades. In this context, it matters to discuss John Rawls’s influential difference principle. According to the maximin criterion put forth by Rawls, it does not suffice that no one becomes worse off; those who are worse off must also become better off than they are. Here, we note that the existence and growth of inequality find no opposition in the maximin rule. Despite appearances, strictly speaking it merely introduces a factor of social compensation, a sort of “assistencialism” to the victims of the greatest inequality. Even the most robust formulation of the principle of difference, according to which the greatest advantage to the less advantaged is indispensable, does not per se preclude an aggregate growth of inequalities. It seems clear that it was an egalitarian goal what Rawls had in mind in A Theory of Justice. Rawls’s critical comments on welfare capitalism must indeed not be forgotten—especially in his further explanations about the application of the principles of justice in a property-owning democracy. Here, as in liberal socialism, the dispersion of property, capital and resources prevents economic and political powers from being concentrated into the hands of a minority. However, the egalitarian aim does not strictly follow from the difference principle as stated, whether taken literally as an application of the maximin rule or inferring from its strongest formulation. A reformulation that does justice to the egalitarian aim of the principle of difference is, however, possible: namely, a degrowthist reformulation, truly requiring a degrowth in accumulation and inequalities, making explicit a brake clause that hinders the aggregate growth of inequalities. Such a degrowthist conception of the difference principle may justify some concrete rules that are able to enforce the egalitarian commitments of social democracy.
Ring opening reactions of nitrogen heterocycles
Authors: Smolobochkin Andrey V. , Gazizov Almir S. , Burilov Alexander R. , Pudovik Mikhail A. , Sinyashin Oleg G. 
Published: June 2019

Published data on ring opening reactions of nitrogen-containing cyclic compounds resulting in various acyclic products are integrated and systematized. The reactions of common five-, six- and seven-membered nitrogen heterocycles containing one to four nitrogen atoms in the ring and having various structures (mononuclear, polynuclear, fused, saturated, unsaturated and aromatic) are considered. Special emphasis is made on the potential of nitrogen heterocycles for the synthesis of polyfunctional open-chain compounds. The advantages and disadvantages of the proposed approaches are noted. Data on the biological activities of some ring opening products of the title heterocycles are presented. The text is arranged according to the type of reagents and catalysts used.The bibliography includes 196 references.
Evidence for distinct biodevelopmental influences on male sexual orientation
Authors: Swift-Gallant Ashlyn , Coome Lindsay A. , Aitken Madison , Monks D. Ashley , VanderLaan Doug P. 
Published: June 2019

Significance
Studying individual differences in gender and sexual orientation provides insight into how early-life biology shapes brain and behavior. The literature identifies multiple biodevelopmental influences on male sexual orientation, but these influences are generally studied individually, and the potential for association or interaction between them remains largely unexplored. We hypothesized that distinct biodevelopmental pathways correspond to specific subgroups of nonheterosexual men. We present evidence that nonheterosexual men can be categorized into at least four subgroups based on established biomarkers, and these biodevelopmental pathways differentially relate to gender expression and personality traits. These findings indicate individual differences in biodevelopmental pathways of male sexual orientation. They also illustrate the value of latent profile analyses for studying individual differences.
Exploration of the chemical space and its three historical regimes
Authors: Llanos Eugenio J. , Leal Wilmer , Luu Duc H. , Jost Jürgen , Stadler Peter F. , Restrepo Guillermo 
Published: June 2019

Significance
We found that the number of new chemical compounds has grown exponentially with a 4.4% annual production rate from 1800 to 2015 not even affected by World Wars. There are three distinct growth regimes: proto-organic, organic, and organometallic, with decreasing variability in the production of compounds over time. Contrary to the belief that organic synthesis developed only after 1828, synthesis had been a key provider of new compounds already at the beginning of the 19th century. By 1900, it became the established tool to report new compounds. We found that chemists are conservative when selecting starting materials and that despite the growing production of new compounds, most of them belong to a restricted set of chemical compositions.
Common neural code for reward and information value
Authors: Kobayashi Kenji , Hsu Ming 
Published: June 2019

Significance
It is more important than ever to seek information adaptively. While it is optimal to acquire information based solely on its instrumental benefit, humans also often acquire useless information because of psychological motives, such as curiosity and pleasure of anticipation. Here we show that instrumental and noninstrumental motives are multiplexed in subjective value of information (SVOI) signals in human brains. Subjects’ information seeking in an economic decision-making task was captured by a model of SVOI, which reflects not only information’s instrumental benefit but also utility of anticipation it provides. SVOI was represented in traditional value regions, sharing a common code with more basic reward value. This demonstrates that valuation system combines multiple motives to drive information-seeking behavior.
Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1–induced mechanisms
Authors: Helyes Zsuzsanna , Tékus Valéria , Szentes Nikolett , Pohóczky Krisztina , Botz Bálint , Kiss Tamás , Kemény Ágnes , Környei Zsuzsanna , Tóth Krisztina , Lénárt Nikolett , Ábrahám Hajnalka , Pinteaux Emmanuel , Francis Sheila , Sensi Serena , Dénes Ádám , Goebel Andreas 
Published: June 2019

Significance
Complex regional pain syndrome (CRPS) is a poorly understood painful condition, which typically arises after distal limb trauma; 20% of patients may develop lifelong severe incessant pain with few therapeutic options. In this study, we show that immunoglobulin G autoantibodies from patients with severe, persistent CRPS, on transfer to hind paw-injured mice, elicit important features of the clinical condition and profound glial activation in pain-related brain regions. Blockade of the proinflammatory cytokine interleukin-1 (IL-1) both prevents and reverses these changes. Our findings suggest that antibody-mediated autoimmunity contributes to the development of severe CRPS after injury and that blockade of IL-1 actions may be an attractive therapeutic prospect. Investigation of autoantibody contribution to other unexplained chronic pain syndromes seems warranted.
Education rather than age structure brings demographic dividend
Authors: Lutz Wolfgang , Crespo Cuaresma Jesus , Kebede Endale , Prskawetz Alexia , Sanderson Warren C. , Striessnig Erich 
Published: June 2019

SignificanceGlobal environmental change and discussions about the drivers of international migration lead to renewed interest in population growth and global demographic change. The notion of the demographic dividend was introduced to highlight the benefits of fertility decline, yet, among African leaders, it is also often interpreted as describing the benefits of their youthful populations. Due to its controversial nature, the topic of population was not explicitly included in the Sustainable Development Goals. In this controversial discussion, this paper provides a systematic reassessment about what aspects of demographic change have beneficial consequences for economic growth and sustainable development.
The isoprenoid alcohol pathway, a synthetic route for isoprenoid biosynthesis
Authors: Clomburg James M. , Qian Shuai , Tan Zaigao , Cheong Seokjung , Gonzalez Ramon 
Published: June 2019

Significance
We have demonstrated the design, prototyping, and implementation of a non-natural route to isoprenoid biosynthesis, termed the isoprenoid alcohol (IPA) pathway. Opposed to working within the confines of native metabolic pathways, our approach of utilizing all available biochemical reactions identified a synthetic route to isoprenoid compounds that is both different and provides a more energy-efficient pathway compared with native isoprenoid biosynthesis. By improving the overall pathway design, the IPA pathway has the potential to facilitate the synthesis of a diverse range of isoprenoid compounds at high product titers and yields.
Bioinspired inner microstructured tube controlled capillary rise
Authors: Li Chuxin , Dai Haoyu , Gao Can , Wang Ting , Dong Zhichao , Jiang Lei 
Published: June 2019

Significance
Liquid manipulation in tubes or pipes is greatly important for microfluidic chips, artificial blood vessels, dental suction, medical injection, oil–water separators, and biochemical analysis. Spontaneous and directional liquid transport has attracted great interest in recent years. However, existing spontaneous liquid transport systems still perform at low speeds and focus on precursor film spreading or drop motion. In this study, we propose an inner peristome-mimetic structured tube with controlled capillary rise and siphon diode behaviors. Our method makes it possible to actuate a larger amount of bulk liquid to transfer spontaneously and continuously in an antigravity direction, develops a generation of microfluidic devices, and is able to function without complex accessories, such as pumps or valves.
Massively parallel screening of synthetic microbial communities
Authors: Kehe Jared , Kulesa Anthony , Ortiz Anthony , Ackerman Cheri M. , Thakku Sri Gowtham , Sellers Daniel , Kuehn Seppe , Gore Jeff , Friedman Jonathan , Blainey Paul C. 
Published: June 2019

Significance
Microbial communities have many applications, but current experimental strategies to investigate their behavior are limited by the combinatorial complexity of interactions between species. Here, we introduce a platform to automatically construct and test synthetic communities of microbes from a set of input species at a scale of ∼100,000 communities per day. As a first demonstration, we discovered specific compositions of bacteria isolated from local soil that promote the growth of a model plant symbiont. More broadly, our platform can be adopted for the discovery of microbial consortia with many useful properties, such as suppression of pathogens or degradation of recalcitrant substrates for use in biofuel production or environmental remediation.
Drought suppresses soil predators and promotes root herbivores in mesic, but not in xeric grasslands
Authors: Franco André L. C. , Gherardi Laureano A. , de Tomasel Cecilia M. , Andriuzzi Walter S. , Ankrom Katharine E. , Shaw E. Ashley , Bach Elizabeth M. , Sala Osvaldo E. , Wall Diana H. 
Published: June 2019

SignificanceTemporal and spatial variation in precipitation affect the functional composition of biological communities and ecosystems. Belowground, these changes disrupt the fragile balance between root herbivores, which are major constraints of ecosystem primary production, and their predators. We provide evidence that droughts and deluges alter the functional composition of soil nematode communities depending on the long-term mean annual precipitation (MAP) along a gradient from arid to moist grasslands. The abundance of root-feeding nematodes increased under drought following reductions in the number of predators. These responses increased in magnitude along the MAP gradient, demonstrating that climate change can tip the nematode predator-prey balance and result in higher abundance of root herbivores with potentially important implications for mesic grasslands.
Elevated dopamine signaling from ventral tegmental area to prefrontal cortical parvalbumin neurons drives conditioned inhibition
Authors: Yan Rongzhen , Wang Tianyu , Zhou Qiang 
Published: June 2019

Significance
Suppression of a learned response is critical to survival and adaptation and is impaired in various diseases. Conditioned inhibition is proposed to require learning and inhibitory processes, but its exact nature is poorly understood. Here we studied safety cue-triggered fear suppression and found that its learning process requires plasticity in the ventral tegmental area (VTA), leading to an enhanced dopaminergic (DA) neuron activity by safety cue, and its inhibitory process requires VTA DA neuron inputs to parvalbumin neurons in the dorsomedial prefrontal cortex (dmPFC) to reduce dmPFC activity and fear responses. This DA-dependent learning process is impaired in a posttraumatic stress disorder model. Thus, conditioned inhibition requires complex interactions between DA and GABAergic signaling to suppress learned responses.
Endothelial cell Piezo1 mediates pressure-induced lung vascular hyperpermeability via disruption of adherens junctions
Authors: Friedrich Emily E. , Hong Zhigang , Xiong Shiqin , Zhong Ming , Di Anke , Rehman Jalees , Komarova Yulia A. , Malik Asrar B. 
Published: June 2019

SignificanceIncreased hydrostatic pressure in lung capillaries experienced during high altitude, head trauma, and left heart failure can lead to disruption of lung endothelial barrier and edema formation. We identified Piezo1 as a mechanical sensor responsible for endothelial barrier breakdown (barotrauma) secondary to reduced expression of the endothelial adherens junction proteins VE-cadherin, β-catenin, and p120-catenin. Endothelial-specific deletion or pharmacological inhibition of Piezo1 prevented lung capillary leakage, suggesting a therapeutic approach for preventing edema and associated lung failure.
Shear stress regulation of miR-93 and miR-484 maturation through nucleolin
Authors: Gongol Brendan , Marin Traci , Zhang Jiao , Wang Shen-Chih , Sun Wei , He Ming , Chen Shanshan , Chen Lili , Li Jie , Liu Jun-Hui , Martin Marcy , Han Yue , Kang Jian , Johnson David A. , Lytle Christian , Li Yi-Shuan , Huang Po-Hsun , Chien Shu , Shyy John Y.-J. 
Published: June 2019

Significance
This work identifies a mechanism by which atheroprone oscillatory shear and atheroprotective pulsatile shear differentially regulate microRNA (miR) biogenesis in the vascular endothelium. Nonphosphorylated nucleolin facilitates the maturation of miR-93 and miR-484, which in turn target Krüpple-like factor 2 and endothelial nitric oxide synthase mRNAs. The translational significance of these findings is provided by the identification of elevated levels of miR-93 and miR-484 in sera from patients with coronary artery disease.