bluuebunny/crossref_metadata_2025 huggingface dataset:
Ignorance Is Not Bliss: If We Don’t Understand Hypoactive Sexual Desire Disorder, How Can Flibanserin Treat It? Commentary
Authors: Anderson Ryan , Moffatt Claire E.
Published: February 2018

Background

Female sexual dysfunction (FSD) affects as many as 1 in every 3 women, with a significant portion of these with hypoactive sexual desire disorder (HSDD). These figures alone present significant psychological and pharmacologic challenges. Partly in response to this situation, in 2015 the US Food and Drug Administration approved flibanserin for the treatment of HSDD. This approval has drawn criticism on the grounds of efficacy and necessity.

Aim

To better inform potential consumers about FSD, flibanserin and other interventions for the treatment of HSDD, the importance of understanding the mechanism of FSD, and the efficacy of flibanserin and to review existing relevant knowledge.

Methods

A literature review of extant clinic studies and theoretical discussion articles was performed.

Outcomes

Efficacy of flibanserin for addressing symptoms associated with HSDD in premenopausal women.

Results

Extant literature and empirical evidence suggest that the efficacy of flibanserin for the treatment of HSDD in premenopausal women is at least questionable.

Clinical Translation

Clinicians considering the prescription of flibanserin would be well advised to appreciate some of the controversies concerning the efficacy of the drug.

Strengths and Limitations

The prohibitive usage guidelines, tenuous risk-benefit profile, and considerable cost of use of flibanserin are each worthy of consideration. Flibanserin thus far has been trialed in only a narrow patient range: premenopausal women in long-term relationships with acquired or generalized HSDD.

Conclusions

Although we acknowledge that the discovery and use of flibanserin constitute a compelling narrative, we conclude by questioning the specific efficacy and necessity of flibanserin in providing a treatment for HSDD in women.
Dose‐Response Effects of Tai Chi and Physical Therapy Exercise Interventions in Symptomatic Knee Osteoarthritis
Authors: Lee Augustine C. , Harvey William F. , Price Lori Lyn , Han Xingyi , Driban Jeffrey B. , Iversen Maura D. , Desai Sima A. , Knopp Hans E. , Wang Chenchen
Published: February 2018

Background

Therapeutic exercise is a currently recommended nonpharmacological treatment for knee osteoarthritis (KOA). The optimal treatment dose (frequency or duration) has not been determined.

Objective

To examine dose‐response relationships, minimal effective dose, and baseline factors associated with the timing of response from 2 exercise interventions in KOA.

Design

Secondary analysis of a single‐blind, randomized trial comparing 12‐week Tai Chi and physical therapy exercise programs (Trial Registry #NCT01258985).

Setting

Urban tertiary care academic hospital

Participants

A total of 182 participants with symptomatic KOA (mean age 61 years; BMI 32 kg/m2, 70% female; 55% white).

Methods

We defined dose as cumulative attendance‐weeks of intervention, and treatment response as ≥20% and ≥50% improvement in pain and function. Using log‐rank tests, we compared time‐to‐response between interventions, and used Cox regression to examine baseline factors associated with timing of response, including physical and psychosocial health, physical performance, outcome expectations, self‐efficacy, and biomechanical factors.

Main Outcome Measures

Weekly Western Ontario and McMasters Osteoarthritis Index (WOMAC) pain (0‐500) and function (0‐1700) scores.

Results

Both interventions had an approximately linear dose‐response effect resulting in a 9‐ to 11‐point reduction in WOMAC pain and a 32‐ to 41‐point improvement in function per attendance‐week. There was no significant difference in overall time‐to‐response for pain and function between treatment groups. Median time‐to‐response for ≥20% improvement in pain and function was 2 attendance‐weeks and for ≥50% improvement was 4‐5 attendance‐weeks. On multivariable models, outcome expectations were independently associated with incident function response (hazard ratio = 1.47, 95% confidence interval 1.004‐2.14).

Conclusions

Both interventions have approximately linear dose‐dependent effects on pain and function; their minimum effective doses range from 2‐5 weeks; and patient perceived benefits of exercise influence the timing of response in KOA. These results may help clinicians to optimize patient‐centered exercise treatments and better manage patient expectations.

Level of Evidence

II
Interview with Christoph Geyer
Authors: Howell Elizabeth , Geyer Christoph
Published: February 2018

Reinforced Plastics spoke with Christoph Geyer from SAERTEX about their materials and their impact.
The Normative Justification of Integrative Stakeholder Engagement: A Habermasian View on Responsible Leadership
Authors: Patzer Moritz , Voegtlin Christian , Scherer Andreas Georg
Published: February 2018

The transition from modern to postmodern society leads to changing expectations about the purpose and responsibility of leadership. Habermas’s social theory provides a useful analytical tool for understanding current societal transition processes and exploring their implications for the responsibility of business vis-à-vis society. We argue that integrative responsible leadership, in particular, can contribute to the reconciliation of business with societal goals. Integrative responsible leadership understood in a Habermasian way is not only a strategic endeavor but also a communicative endeavor. An essential part of integrative responsible leadership in light of the current societal transformation processes is the facilitation of discourses about a shared base of norms and values. This is exemplified alongside current societal developments like the European migration crisis or the emerging nationalist and fundamentalist movements in some countries. We specify how and when leadership should resort to communicative action and discuss the implications for leadership.
Capacity development and Indigenous social enterprise: The case of the Rirratjingu clan in northeast Arnhem Land
Authors: Spencer Rochelle , Brueckner Martin , Wise Gareth , Marika Bundak
Published: February 2018

With the widespread shift from models of welfare to business-led development, capacity development offers a useful lens from which to consider the emergence of Indigenous social enterprise as a business-led development approach. We explore capacity development from the international development literature and identify capacity development principles in the context of an Indigenous social enterprise in remote northeast Arnhem Land. Here, Aboriginal Australians continue to experience poverty and marginalisation. This paper provides an ethnographic example of the relationship between Indigenous social enterprise and capacity development. Identifying principles of capacity development in this rich context reveals the remit of the Indigenous social enterprise privileges environmental stewardship and cultural maintenance.
Current levels of gonorrhoea screening in MSM in Belgium may have little effect on prevalence: a modelling study
Authors: Buyze J. , Vanden Berghe W. , Hens N. , Kenyon C.
Published: February 2018

There is considerable uncertainty as to the effectiveness of Neisseria gonorrhoeae (NG) screening in men who have sex with men. It is important to ensure that screening has benefits that outweigh the risks of increased antibiotics resistance. We develop a mathematical model to estimate the effectiveness of screening on prevalence. Separable Temporal Exponential family Random Graph Models are used to model the sexual relationships network, both with main and casual partners. Next, the transmission of Gonorrhoea is simulated on this network. The models are implemented using the R package ‘statnet’, which we adapted among other things to incorporate infection status at the pharynx, urethra and rectum separately and to distinguish between anal sex, oral sex and rimming. The different screening programmes compared are no screening, 3.5% of the population screened, 32% screened and 50% screened. The model simulates day-by-day evolution for 10 years of a population of 10 000. If half of the population would be screened, the prevalence in the pharynx decreases from 11.9% to 10.2%. We conclude that the limited impact of screening on NG prevalence may not outweigh the increased risk of antibiotic resistance.
Short periods of darkness fail to restore visual or neural plasticity in adult cats
Authors: HOLMAN KAITLYN D. , DUFFY KEVIN R. , MITCHELL DONALD E.
Published: February 2018

It has been shown that the visual acuity loss experienced by the deprived eye of kittens following an early period of monocular deprivation (MD) can be alleviated rapidly following 10 days of complete darkness when imposed even as late as 14 weeks of age. To examine whether 10 days of darkness conferred benefits at any age, we measured the extent of recovery of the visual acuity of the deprived eye following the darkness imposed on adult cats that had received the same early period of MD as used in prior experiments conducted on kittens. Parallel studies conducted on different animals examined the extent to which darkness changed the magnitude of the MD-induced laminar differences of the cell soma size and immunoreactivity for the neurofilament (NF) protein in the dorsal lateral geniculate nucleus (dLGN). The results indicated that 10 days of darkness imposed at one year of age neither alleviated the acuity loss of the deprived eye induced by an earlier period of MD nor did it decrease the concurrent lamina differences of the soma size or NF loss in the dLGN.
Melanopsin expression in the cornea
Authors: DELWIG ANTON , CHANEY SHAWNTA Y. , BERTKE ANDREA S. , VERWEIJ JAN , QUIRCE SUSANA , LARSEN DELAINE D. , YANG CINDY , BUHR ETHAN , VAN GELDER RUSSELL , GALLAR JUANA , MARGOLIS TODD , COPENHAGEN DAVID R.
Published: February 2018

A unique class of intrinsically photosensitive retinal ganglion cells in mammalian retinae has been recently discovered and characterized. These neurons can generate visual signals in the absence of inputs from rods and cones, the conventional photoreceptors in the visual system. These light sensitive ganglion cells (mRGCs) express the non-rod, non-cone photopigment melanopsin and play well documented roles in modulating pupil responses to light, photoentrainment of circadian rhythms, mood, sleep and other adaptive light functions. While most research efforts in mammals have focused on mRGCs in retina, recent studies reveal that melanopsin is expressed in non-retinal tissues. For example, light-evoked melanopsin activation in extra retinal tissue regulates pupil constriction in the iris and vasodilation in the vasculature of the heart and tail. As another example of nonretinal melanopsin expression we report here the previously unrecognized localization of this photopigment in nerve fibers within the cornea. Surprisingly, we were unable to detect light responses in the melanopsin-expressing corneal fibers in spite of our histological evidence based on genetically driven markers and antibody staining. We tested further for melanopsin localization in cell bodies of the trigeminal ganglia (TG), the principal nuclei of the peripheral nervous system that project sensory fibers to the cornea, and found expression of melanopsin mRNA in a subset of TG neurons. However, neither electrophysiological recordings nor calcium imaging revealed any light responsiveness in the melanopsin positive TG neurons. Given that we found no light-evoked activation of melanopsin-expressing fibers in cornea or in cell bodies in the TG, we propose that melanopsin protein might serve other sensory functions in the cornea. One justification for this idea is that melanopsin expressed inDrosophilaphotoreceptors can serve as a temperature sensor.
Conservation implications of spatial genetic structure in two species of oribatid mites from the Antarctic Peninsula and the Scotia Arc
Authors: van Vuuren Bettine Jansen , Lee Jennifer E. , Convey Peter , Chown Steven L.
Published: February 2018

Mitochondrial and nuclear sequence data from two Antarctic ameronothroid mites, Halozetes belgicae and Alaskozetes antarcticus, were used to address three key questions important for understanding both the evolution of biodiversity and its future conservation in the Antarctic Peninsula Region: i) Do populations of mites across the Antarctic Peninsula and Scotia Arc constitute distinct genetic lineages? ii) What implications does the spatial genetic structure in these species have for current understanding of the region’s glacial history? iii) What are the conservation implications of these findings? Our results indicate that both mite species have been present in the Antarctic since at least the Pliocene. At the regional scale, both species are comprised of a number of divergent, but sympatric, lineages that are genetically as distinct as some species within the genera Halozetes and Alaskozetes. At the local scale, complex structure suggests limited and stochastic post-Holocene dispersal. For both species, considerable spatial genetic structure exists across the region, similar to that found in other terrestrial invertebrates. These results support the implementation of stringent biosecurity measures for moving between the Scotia Arc islands and the Antarctic Peninsula, and throughout the latter, to conserve both evolutionary history and future evolutionary trajectories.
Towns in Victorian England and Wales: a new classification
Authors: SMITH HARRY , BENNETT ROBERT J. , RADICIC DRAGANA
Published: February 2018

This article describes the creation of a new urban classification based on the 1891 census of England and Wales. It is the first attempt to use the recently available electronic version of the census (I-CeM) to classify all large towns in late Victorian England and Wales on their economic structure. Where previous scholars were restricted by the form of occupation data contained in the published census reports, I-CeM allows manipulation of the data in order to aggregate urban units and examine their occupational structures in great detail. The classification is then used to compare key socio-economic characteristics of different towns.
Chronic disease burden predicts food insecurity among older adults
Authors: Jih Jane , Stijacic-Cenzer Irena , Seligman Hilary K , Boscardin W John , Nguyen Tung T , Ritchie Christine S
Published: February 2018

Objective

Increased out-of-pocket health-care expenditures may exert budget pressure on low-income households that leads to food insecurity. The objective of the present study was to examine whether older adults with higher chronic disease burden are at increased risk of food insecurity.

Design

Secondary analysis of the 2013 Health and Retirement Study (HRS) Health Care and Nutrition Study (HCNS) linked to the 2012 nationally representative HRS.

Setting

USA.

Subjects

Respondents of the 2013 HRS HCNS with household incomes <300 % of the federal poverty line (n 3552). Chronic disease burden was categorized by number of concurrent chronic conditions (0–1, 2–4, ≥5 conditions), with multiple chronic conditions (MCC) defined as ≥2 conditions.

Results

The prevalence of food insecurity was 27·8 %. Compared with those having 0–1 conditions, respondents with MCC were significantly more likely to report food insecurity, with the adjusted odds ratio for those with 2–4 conditions being 2·12 (95 % CI 1·45, 3·09) and for those with ≥5 conditions being 3·64 (95 % CI 2·47, 5·37).

Conclusions

A heavy chronic disease burden likely exerts substantial pressure on the household budgets of older adults, creating an increased risk for food insecurity. Given the high prevalence of food insecurity among older adults, screening those with MCC for food insecurity in the clinical setting may be warranted in order to refer to community food resources.
Medicare and the care of First Nations, Métis and Inuit
Authors: Lavoie Josée G.
Published: February 2018

TheCanada Health Act1984 (CHA) is considered foundational to Canada’s publicly funded health care system (known as Medicare). The CHA provides for the federal transfer of funding to the provinces/territories, in exchange for provincial/territorial adherence to Medicare’s key principles of universality; comprehensiveness; portability; accessibility; and, public administration. Medicare is a decentralized health care system, managed independently by Canada’s 10 provincial and three territorial governments, allowing for regional adaptations to fit varying degrees of urbanity, remoteness and needs. The Act is silent on its relationship to the Indigenous health care system – what some have described as Canada’s 14th health care system. The CHA has not kept pace with Indigenous self-government activities that have since spread across Canada. It has unfortunately crystallized the federal/provincial/territorial/Indigenous jurisdictional fragmentation that perpetuates health inequities and has failed to clarify these jurisdictions’ obligations towards Indigenous peoples. As a result of these omissions, access to health services remains a concern for many Indigenous Canadians, resulting in poorer outcomes and premature mortality. In this paper, I argue that Medicare renewal must: make an explicit commitment to Indigenous health equity; clarify jurisdictional obligations; establish effective mechanisms for addressing areas of jurisdictional dispute and/or confusion; and explicitly recognize First Nations and Inuit health care services as integral yet distinct systems, that nevertheless must be welcomed to seamlessly work with provincial health care systems to ensure continuity of care.
First Near-Global Measurements of Isotopic Nitrous Oxide
Authors: Cook Terri
Published: February 2018

By harnessing satellite data collected from low-Earth orbit, scientists can now track the distribution of atmospheric nitrous oxide and its isotopes.
Seeking Salt That Surfaces from Europa’s Hidden Ocean
Authors: Stanley Sarah
Published: February 2018

Irradiation-induced color changes in sodium chloride could reveal whether it came from ocean water mixing with surface water, a key component of the moon’s potential to support life.
Trump’s Address to Congress Largely Ignores Science
Authors: Showstack Randy
Published: February 2018

Speech touts ending “the war on coal” but makes no reference to climate change.
Non-coding RNA dysregulation in the amygdala region of schizophrenia patients contributes to the pathogenesis of the disease
Authors: Liu Yichuan , Chang Xiao , Hahn Chang-Gyu , Gur Raquel E. , Sleiman Patrick A. M. , Hakonarson Hakon
Published: February 2018

Schizophrenia (SCZ) is a neuropsychiatric disorder with a complex genetic etiology. The redundancy of the gene networks underlying SCZ indicates that many gene combinations have the potential to cause a system dysfunction that can manifest as SCZ or a related neurodevelopmental disorder. Recent studies show that small non-coding microRNA (miRNA) and long non-coding RNA (lncRNA) are important factors in shaping these networks and are dynamically regulated by neuronal activation. We investigated the genome-wide transcription profiles of 46 human amygdala samples obtained from 22 SCZ patients and 24 healthy controls. Using RNA sequencing (RNA-seq), we determined lncRNA expression levels in all samples and generated miRNA profiles for 27 individuals (13 cases and 14 controls). Previous studies have identified differentially expressed miRNAs in SCZ, including miR-132, miR-212, and miR-34a/miR-34c. Here we report differential expression of a novel miRNA, miR1307, in SCZ. Notably, miR1307 maps to a locus previously associated with SCZ through GWAS. Additionally, one lncRNA that was overexpressed in SCZ, AC005009.2, also maps to a region previously associated with SCZ based on GWAS and overlapped SCZ-related genes. The results were replicated in a large independent data set of 254 dorsolateral prefrontal cortex samples from the CommonMind consortium. Taken together, these results suggest that miRNA and lncRNAs are important contributors to the pathogenesis of SCZ.
Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8
Authors: McElroy Susan L. , Winham Stacey J. , Cuellar-Barboza Alfredo B. , Colby Colin L. , Ho Ada Man-Choi , Sicotte Hugues , Larrabee Beth R. , Crow Scott , Frye Mark A. , Biernacka Joanna M.
Published: February 2018

Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed a meta-analysis of the Mayo and GAIN results. The meta-analysis provided genome-wide significant evidence of association between single nucleotide polymorphisms (SNPs) in PRR5-ARHGAP8 and BE in BD cases (rs726170 OR = 1.91, P = 3.05E-08). In the meta-analysis comparing cases with BD with comorbid BE vs. non-BD controls, a genome-wide significant association was observed at SNP rs111940429 in an intergenic region near PPP1R2P5 (p = 1.21E-08). PRR5-ARHGAP8 is a read-through transcript resulting in a fusion protein of PRR5 and ARHGAP8. PRR5 encodes a subunit of mTORC2, a serine/threonine kinase that participates in food intake regulation, while ARHGAP8 encodes a member of the RhoGAP family of proteins that mediate cross-talk between Rho GTPases and other signaling pathways. Without BE information in controls, it is not possible to determine whether the observed association reflects a risk factor for BE in general, risk for BE in individuals with BD, or risk of a subtype of BD with BE. The effect of PRR5-ARHGAP8 on BE risk thus warrants further investigation.
21st Century drought-related fires counteract the decline of Amazon deforestation carbon emissions
Authors: Aragão Luiz E. O. C. , Anderson Liana O. , Fonseca Marisa G. , Rosan Thais M. , Vedovato Laura B. , Wagner Fabien H. , Silva Camila V. J. , Silva Junior Celso H. L. , Arai Egidio , Aguiar Ana P. , Barlow Jos , Berenguer Erika , Deeter Merritt N. , Domingues Lucas G. , Gatti Luciana , Gloor Manuel , Malhi Yadvinder , Marengo Jose A. , Miller John B. , Phillips Oliver L. , Saatchi Sassan
Published: February 2018

Tropical carbon emissions are largely derived from direct forest clearing processes. Yet, emissions from drought-induced forest fires are, usually, not included in national-level carbon emission inventories. Here we examine Brazilian Amazon drought impacts on fire incidence and associated forest fire carbon emissions over the period 2003–2015. We show that despite a 76% decline in deforestation rates over the past 13 years, fire incidence increased by 36% during the 2015 drought compared to the preceding 12 years. The 2015 drought had the largest ever ratio of active fire counts to deforestation, with active fires occurring over an area of 799,293 km2. Gross emissions from forest fires (989 ± 504 Tg CO2 year−1) alone are more than half as great as those from old-growth forest deforestation during drought years. We conclude that carbon emission inventories intended for accounting and developing policies need to take account of substantial forest fire emissions not associated to the deforestation process.
A transcriptomic atlas of aged human microglia
Authors: Olah Marta , Patrick Ellis , Villani Alexandra-Chloe , Xu Jishu , White Charles C. , Ryan Katie J. , Piehowski Paul , Kapasi Alifiya , Nejad Parham , Cimpean Maria , Connor Sarah , Yung Christina J. , Frangieh Michael , McHenry Allison , Elyaman Wassim , Petyuk Vlad , Schneider Julie A. , Bennett David A. , De Jager Philip L. , Bradshaw Elizabeth M.
Published: February 2018

With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia—the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative disease. Here, we establish the set of genes that is preferentially expressed by microglia in the aged human brain. This HuMi_Aged gene set captures a unique phenotype, which we confirm at the protein level. Furthermore, we find this gene set to be enriched in susceptibility genes for Alzheimer’s disease and multiple sclerosis, to be increased with advancing age, and to be reduced by the protective APOEε2 haplotype. APOEε4 has no effect. These findings confirm the existence of an aging-related microglial phenotype in the aged human brain and its involvement in the pathological processes associated with brain aging.
Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice
Authors: Wang Xiao , Li Fengfeng , Xie Liang , Crane Janet , Zhen Gehua , Mishina Yuji , Deng Ruoxian , Gao Bo , Chen Hao , Liu Shen , Yang Ping , Gao Manman , Tu Manli , Wang Yiguo , Wan Mei , Fan Cunyi , Cao Xu
Published: February 2018

Acquired heterotopic ossification (HO) is a painful and debilitating disease characterized by extraskeletal bone formation after injury. The exact pathogenesis of HO remains unknown. Here we show that TGF-β initiates and promotes HO in mice. We find that calcified cartilage and newly formed bone resorb osteoclasts after onset of HO, which leads to high levels of active TGF-β that recruit mesenchymal stromal/progenitor cells (MSPCs) in the HO microenvironment. Transgenic expression of active TGF-β in tendon induces spontaneous HO, whereas systemic injection of a TGF-β neutralizing antibody attenuates ectopic bone formation in traumatic and BMP-induced mouse HO models, and in a fibrodysplasia ossificans progressive mouse model. Moreover, inducible knockout of the TGF-β type II receptor in MSPCs inhibits HO progression in HO mouse models. Our study points toward elevated levels of active TGF-β as inducers and promoters of ectopic bone formation, and suggest that TGF-β might be a therapeutic target in HO.
AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle
Authors: Kim Young-Chae , Seok Sunmi , Byun Sangwon , Kong Bo , Zhang Yang , Guo Grace , Xie Wen , Ma Jian , Kemper Byron , Kemper Jongsook Kim
Published: February 2018

Phosphatidylcholines (PC) and S-adenosylmethionine (SAM) are critical determinants of hepatic lipid levels, but how their levels are regulated is unclear. Here, we show that Pemt and Gnmt, key one-carbon cycle genes regulating PC/SAM levels, are downregulated after feeding, leading to decreased PC and increased SAM levels, but these effects are blunted in small heterodimer partner (SHP)-null or FGF15-null mice. Further, aryl hydrocarbon receptor (AhR) is translocated into the nucleus by insulin/PKB signaling in the early fed state and induces Pemt and Gnmt expression. This induction is blocked by FGF15 signaling-activated SHP in the late fed state. Adenoviral-mediated expression of AhR in obese mice increases PC levels and exacerbates steatosis, effects that are blunted by SHP co-expression or Pemt downregulation. PEMT, AHR, and PC levels are elevated in simple steatosis patients, but PC levels are robustly reduced in steatohepatitis-fibrosis patients. This study identifies AhR and SHP as new physiological regulators of PC/SAM levels.
The lymphocyte-to-monocyte ratio is a superior predictor of overall survival compared to established biomarkers in HCC patients undergoing liver resection
Authors: Yang Yu-Ting , Jiang Jing-Hang , Yang Hao-Jie , Wu Zhi-jun , Xiao Ze-Min , Xiang Bang-De
Published: February 2018

The aim of this study was to investigate the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients undergoing hepatectomy and to compare it to established biomarkers including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Medical records were retrospectively analyzed for 652 HCC patients undergoing hepatectomy at the Affiliated Tumor Hospital of Guangxi Medical University and the First People’s Hospital of Changde between April 2004 to April 2012. The correlation between the LMR and clinical variables were analyzed in Kaplan-Meier log-rank survival analysis and then multivariate Cox regression models trying to find relation with disease-free survival (DFS) and overall survival (OS). The area under the ROC curve (AUC) of the LMR(AUC:0.627) for predicting long-term survival was greater than that of the NLR(AUC:0.600) and the PLR(AUC:0.520).Multivariate analysis showed LMR to be an independent risk factor for OS (P = 0.002), and the NLR and PLR were not independently significant. Subgroup analysis also showed that LMR was significantly associated with poor DFS and OS in patients positive for HBsAg or with cirrhosis (both P < 0.001).Elevated preoperative LMR is an independently associated with poor OS and DFS in HCC patients following curative resection and appears to be superior to NLR and PLR.
Ginkgolic acid, a sumoylation inhibitor, promotes adipocyte commitment but suppresses adipocyte terminal differentiation of mouse bone marrow stromal cells
Authors: Liu Huadie , Li Jianshuang , Lu Di , Li Jie , Liu Minmin , He Yuanzheng , Williams Bart O. , Li Jiada , Yang Tao
Published: February 2018

Sumoylation is a post-translational modification process having an important influence in mesenchymal stem cell (MSC) differentiation. Thus, sumoylation-modulating chemicals might be used to control MSC differentiation for skeletal tissue engineering. In this work, we studied how the differentiation of mouse bone marrow stromal cells (mBMSCs) is affected by ginkgolic acid (GA), a potent sumoylation inhibitor also reported to inhibit histone acetylation transferase (HAT). Our results show that GA promoted the differentiation of mBMSCs into adipocytes when cultured in osteogenic medium. Moreover, mBMSCs pre-treated with GA showed enhanced pre-adipogenic gene expression and were more efficiently differentiated into adipocytes when subsequently cultured in the adipogenic medium. However, when GA was added at a later stage of adipogenesis, adipocyte maturation was markedly inhibited, with a dramatic down-regulation of multiple lipogenesis genes. Moreover, we found that the effects of garcinol, a HAT inhibitor, differed from those of GA in regulating adipocyte commitment and adipocyte maturation of mBMSCs, implying that the GA function in adipogenesis is likely through its activity as a sumoylation inhibitor, not as a HAT inhibitor. Overall, our studies revealed an unprecedented role of GA in MSC differentiation and provide new mechanistic insights into the use of GA in clinical applications.
Cross-Scale Molecular Analysis of Chemical Heterogeneity in Shale Rocks
Authors: Hao Zhao , Bechtel Hans A. , Kneafsey Timothy , Gilbert Benjamin , Nico Peter S.
Published: February 2018

The organic and mineralogical heterogeneity in shale at micrometer and nanometer spatial scales contributes to the quality of gas reserves, gas flow mechanisms and gas production. Here, we demonstrate two molecular imaging approaches based on infrared spectroscopy to obtain mineral and kerogen information at these mesoscale spatial resolutions in large-sized shale rock samples. The first method is a modified microscopic attenuated total reflectance measurement that utilizes a large germanium hemisphere combined with a focal plane array detector to rapidly capture chemical images of shale rock surfaces spanning hundreds of micrometers with micrometer spatial resolution. The second method, synchrotron infrared nano-spectroscopy, utilizes a metallic atomic force microscope tip to obtain chemical images of micrometer dimensions but with nanometer spatial resolution. This chemically “deconvoluted” imaging at the nano-pore scale is then used to build a machine learning model to generate a molecular distribution map across scales with a spatial span of 1000 times, which enables high-throughput geochemical characterization in greater details across the nano-pore and micro-grain scales and allows us to identify co-localization of mineral phases with chemically distinct organics and even with gas phase sorbents. This characterization is fundamental to understand mineral and organic compositions affecting the behavior of shales.
Mud Banks along the southwest coast of India are not too muddy for plankton
Authors: Jyothibabu R. , Balachandran K. K. , Jagadeesan L. , Karnan C. , Arunpandi N. , Naqvi S. W. A. , Pandiyarajan R. S.
Published: February 2018

Considering Alappuzha Mud Bank in the southern Kerala coast as a typical case of biologically productive Mud Banks that form along the southwest coast of India during the Southwest Monsoon (June - September), the present study addresses several pertinent missing links between the physical environment in Mud Banks and their influence on plankton stock. This study showed that very strong coastal upwelling prevails in the entire study domain during the Southwest Monsoon, which manifests itself in the form of significantly cool, hypoxic and nitrate-rich waters surfacing near the coast. The upwelled water persisting throughout the Southwest Monsoon period was found to have fuelled the exceptionally high phytoplankton stock in the entire study area, including the Mud Bank region. Having accepted that Mud Banks are special because of the calm sea surface conditions and relatively high turbidity level in the water column around them, the present study showed that except at points close to the sea bottom, turbidity level in the Alappuzha Mud Bank was below the critical level to inhibit the plankton stock. The suspended sediments that form in the Mud Bank occasionally could be attributed to the disturbance of the bottom fluid muddy layer and their vertical spurts.
Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation
Authors: Jin Eun-Ju , Ko Hyo Rim , Hwang Inwoo , Kim Byeong-Seong , Choi Jeong-Yun , Park Kye Won , Cho Sung-Woo , Ahn Jee-Yin
Published: February 2018

Neurite growth is controlled by a complex molecular signaling network that regulates filamentous actin (F-actin) dynamics at the growth cone. The evolutionarily conserved ezrin, radixin, and moesin family of proteins tether F-actin to the cell membrane when phosphorylated at a conserved threonine residue and modulate neurite outgrowth. Here we show that Akt binds to and phosphorylates a threonine 573 residue on radixin. Akt-mediated phosphorylation protects radixin from ubiquitin-dependent proteasomal degradation, thereby enhancing radixin protein stability, which permits proper neurite outgrowth and growth cone formation. Conversely, the inhibition of Akt kinase or disruption of Akt-dependent phosphorylation reduces the binding affinity of radixin to F-actin as well as lowers radixin protein levels, resulting in decreased neurite outgrowth and growth cone formation. Our findings suggest that Akt signaling regulates neurite outgrowth by stabilizing radixin interactions with F-actin, thus facilitating local F-actin dynamics.
Development of a mouse IgA monoclonal antibody-based enzyme-linked immunosorbent sandwich assay for the analyses of RBP4
Authors: Lee Nam Seok , Kim Han Soo , Park Se Eun , Blüher Matthias , Park Cheol-Young , Youn Byung-Soo
Published: February 2018

Elevated circulating Retinol-binding protein 4 (RBP4) has been associated with insulin resistance, dyslipidemia, and hypertension. However, many commonly used RBP4 ELISAs have limited dynamic range. We therefore developed an enzyme-linked immunosorbent sandwich assay (ELISA) employing a novel immunoglobulin A (IgA)-type capture mAb called AG102 instead of IgG subtypes, which was selected for its stability, capture efficiency, and specificity for human RBP 4. These features of RBP4 have hampered the development of quantitative immunological assays. Molecular analysis of AG102 revealed IgA heavy and light chains and a J chain, as expected. AG102 demonstrated notable detection of both bacterial- and HEK293-expressed RBP4 in Western blots. Serial and internal deletion experiments suggested that a putative epitope may be located in the first 35 amino acids of the mature RBP4. Compared with commercial ELISAs, the AG102-based system exhibited more significant recovery of RBP4 from serum or urine at any given dilution factor. To substantiate its quantitation capacity, comparison between RBP4 measurements from quantitative western blots and the AG102-based ELISA demonstrated a significant correlation (R2 = 0.859). After measurement for those analytes, our data suggested that IgA-based ELISA could be adapted for quantitative measurement of those analytes existing as major serum proteins or as multi-protein complexes like RBP4.
Molecular detection of field predation among larvae of two ladybird beetles is partially predicted from laboratory experiments
Authors: Rondoni Gabriele , Fenjan Saleh , Bertoldi Valeria , Ielo Fulvio , Djelouah Khaled , Moretti Chiaraluce , Buonaurio Roberto , Ricci Carlo , Conti Eric
Published: February 2018

Despite the fact that natural enemies can synergistically contribute to herbivore pest suppression, sometimes predators engage in intraguild predation (IGP) that might dampen trophic cascades. DNA-based gut-content analysis has become common in assessing trophic connections and biocontrol potential by predators in field systems. Here, we developed a molecular technique that can be used to unravel predation among two ladybirds, Coccinella septempunctata and Hippodamia variegata, and their shared prey, Aphis gossypii. Both ladybirds may provide effective control of the pest. Therefore, understanding their likelihood to engage in IGP is crucial for conservation biological control. Ladybird specimens were collected in melon crop. DNA extraction, primer design and evaluation were conducted. Detectability of prey DNA did not differ significantly between the two ladybirds. H. variegata exhibited higher predation on A. gossypii than C. septempunctata (90.6% vs. 70.9%) and data correction based on DNA detectability confirmed this ranking. IGP was similar among the two species, although corrected data might suggest a stronger predation by C. septempunctata. Intriguingly, IGP by C. septempunctata was lower than predicted by laboratory bioassays, possibly due to the high complexity that arises under field conditions. Implications of our results for biological control and perspectives for ecological network analysis are discussed.
Fly ash incorporated with biocement to improve strength of expansive soil
Authors: Li Mengmeng , Fang Chaolin , Kawasaki Satoru , Achal Varenyam
Published: February 2018

Microbially induced calcium carbonate precipitation (MICP) results in the formation of biocement (BC). This process, also known as biocementation, is recently widely used to improve the strength and durability of building materials including soils. In the present study, effectiveness of biocement as admixture with fly ash (FA) was investigated as first few studies to improve geotechnical properties of expansive soils. Biocement precipitated by Bacillus megaterium was blend with four formulations of fly ash at concentrations of 0, 10, 25 and 50%, namely 0% FABC, 10% FABC, 25% FABC, and 50% FABC, respectively. These formulations were separately added to expansive soils. Specimens with 25% FABC resulted in significant improvement in unconfined compressive strength of expansive soil that was more than two-times higher than control. Further, scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) analyses characterized microstructures of soil specimens, and depicted the process of MICP in improving strength of expansive soils. This research indicates that incorporation of biocement in fly ash is an effective means of increasing the strength of expansive soils.
Exploring an optimal wavelet-based filter for cryo-ET imaging
Authors: Huang Xinrui , Li Sha , Gao Song
Published: February 2018

Cryo-electron tomography (cryo-ET) is one of the most advanced technologies for the in situ visualization of molecular machines by producing three-dimensional (3D) biological structures. However, cryo-ET imaging has two serious disadvantages—low dose and low image contrast—which result in high-resolution information being obscured by noise and image quality being degraded, and this causes errors in biological interpretation. The purpose of this research is to explore an optimal wavelet denoising technique to reduce noise in cryo-ET images. We perform tests using simulation data and design a filter using the optimum selected wavelet parameters (three-level decomposition, level-1 zeroed out, subband-dependent threshold, a soft-thresholding and spline-based discrete dyadic wavelet transform (DDWT)), which we call a modified wavelet shrinkage filter; this filter is suitable for noisy cryo-ET data. When testing using real cryo-ET experiment data, higher quality images and more accurate measures of a biological structure can be obtained with the modified wavelet shrinkage filter processing compared with conventional processing. Because the proposed method provides an inherent advantage when dealing with cryo-ET images, it can therefore extend the current state-of-the-art technology in assisting all aspects of cryo-ET studies: visualization, reconstruction, structural analysis, and interpretation.
Molecular dynamic simulations reveal structural insights into substrate and inhibitor binding modes and functionality of Ecto-Nucleoside Triphosphate Diphosphohydrolases
Authors: Iqbal Jamshed , Shah Syed Jawad Ali
Published: February 2018

Ecto-nucleotidase enzymes catalyze the hydrolysis of extracellular nucleotides to their respective nucleosides. Herein, we place the focus on the elucidation of structural features of the cell surface located ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDase1-3 and 8). The physiological role of these isozymes is crucially important as they control purinergic signaling by modulating the extracellular availability of nucleotides. Since, crystal or NMR structure of the human isozymes are not available – structures have been obtained by homology modeling. Refinement of the homology models with poor stereo-chemical quality is of utmost importance in order to derive reliable structures for subsequent studies. Therefore, the resultant models obtained by homology modelling were refined by running molecular dynamic simulation. Binding mode analysis of standard substrates and of competitive inhibitor was conducted to highlight important regions of the active site involved in hydrolysis of the substrates and possible mechanism of inhibition.
Development of Highly Active Bifunctional Electrocatalyst Using Co3O4 on Carbon Nanotubes for Oxygen Reduction and Oxygen Evolution
Authors: Ahmed Mohammad Shamsuddin , Choi Byungchul , Kim Young-Bae
Published: February 2018

Replacement of precious platinum catalyst with efficient and cheap bifunctional alternatives would be significantly beneficial for electrocatalytic oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) and the application of these catalysts in fuel cells is highly crucial. Despite numerous studies on electrocatalysts, the development of bifunctional electrocatalysts with comparatively better activity and low cost remains a big challenge. In this paper, we report a nanomaterial consisting of nanocactus-shaped Co3O4 grown on carbon nanotubes (Co3O4/CNTs) and employed as a bifunctional electrocatalyst for the simultaneous catalysis on ORR, and OER. The Co3O4/CNTs exhibit superior catalytic activity toward ORR and OER with the smallest potential difference (0.72 V) between the $${{\boldsymbol{E}}}_{{{\boldsymbol{j}}}_{{\bf{10}}}}$$

E

j

10

(1.55 V) for OER and E1/2 (0.83 V) for ORR. Thus, Co3O4/CNTs are promising high-performance and cost-effective bifunctional catalysts for ORR and OER because of their overall superior catalytic activity and stability compared with 20 wt% Pt/C and RuO2, respectively. The superior catalytic activity arises from the unique nanocactus-like structure of Co3O4 and the synergetic effects of Co3O4 and CNTs.
Transcriptome analysis and identification of P450 genes relevant to imidacloprid detoxification in Bradysia odoriphaga
Authors: Chen Chengyu , Wang Cuicui , Liu Ying , Shi Xueyan , Gao Xiwu
Published: February 2018

Pesticide tolerance poses many challenges for pest control, particularly for destructive pests such as Bradysia odoriphaga. Imidacloprid has been used to control B. odoriphaga since 2013, however, imidacloprid resistance in B. odoriphaga has developed in recent years. Identifying actual and potential genes involved in detoxification metabolism of imidacloprid could offer solutions for controlling this insect. In this study, RNA-seq was used to explore differentially expressed genes in B. odoriphaga that respond to imidacloprid treatment. Differential expression data between imidacloprid treatment and the control revealed 281 transcripts (176 with annotations) showing upregulation and 394 transcripts (235 with annotations) showing downregulation. Among them, differential expression levels of seven P450 unigenes were associated with imidacloprid detoxification mechanism, with 4 unigenes that were upregulated and 3 unigenes that were downregulated. The qRT-PCR results of the seven differential expression P450 unigenes after imidacloprid treatment were consistent with RNA-Seq data. Furthermore, oral delivery mediated RNA interference of these four upregulated P450 unigenes followed by an insecticide bioassay significantly increased the mortality of imidacloprid-treated B. odoriphaga. This result indicated that the four upregulated P450s are involved in detoxification of imidacloprid. This study provides a genetic basis for further exploring P450 genes for imidacloprid detoxification in B. odoriphaga.
Synthetic miRNAs induce dual arboviral-resistance phenotypes in the vector mosquito Aedes aegypti
Authors: Yen Pei-Shi , James Anthony , Li Jian-Chiuan , Chen Chun-Hong , Failloux Anna-Bella
Published: February 2018

Mosquito-borne arboviruses are responsible for recent dengue, chikungunya, and Zika pandemics. The yellow-fever mosquito,Aedes aegypti, plays an important role in the transmission of all three viruses. We developed a miRNA-based approach that results in a dual resistance phenotype in mosquitoes to dengue serotype 3 (DENV-3) and chikungunya (CHIKV) viruses. The target viruses are from two distinct arboviral families and the antiviral mechanism is designed to function through the endogenous miRNA pathway in infected mosquitoes. Challenge experiments showed reductions in viral transmission efficiency of transgenic mosquitoes. Several components of mosquito fitness were examined, and transgenic mosquitoes with thePUbpromoter showed minor fitness costs at all developing stages. Further development of these strains with gene editing tools could make them candidates for releases in population replacement strategies for sustainable control of multiple arbovirus diseases.
Development and clinical application of a LC-MS/MS method for simultaneous determination of one-carbon related amino acid metabolites in NTD tissues
Authors: Zhang Min , Wang Lei , Pei Pei , Bao YiHua , Guo Jin , Wang Li , Chang ShaoYan , Xie XiaoLu , Cheng HaiQin , Quan Li , Zhang Ting
Published: February 2018

Simultaneous quantification of 9 pivotal amino acid metabolites in neural tube defect tissues using a LC-MS/MS method.
Correlations and statistical analysis of solvent molecule hydrogen bonding – a case study of dimethyl sulfoxide (DMSO)
Authors: Spiteri L. , Baisch U. , Vella-Zarb L.
Published: February 2018

A statistical study of the correlation between predicted solubility of DMSO solvates and hydrogen bonds between solvent and host molecules.
Surface morphology and adlayer structure of Se on Rh(111)
Authors: Iqbal Shahid , Zan Lingxing , Nardi Elena , Baltruschat Helmut
Published: February 2018

Dependent on potential and deposition conditions, different Se adlayers form on Rh(111) in SeO32− solutions as revealed by CV, STM and AFM.